Portal Vein Embolization and Ligation for Extended Hepatectomy

Portal vein occlusion through embolization or ligation (PVE, PVL) offers the possibility of increasing the future liver remnant (FLR) and thus reducing the risk of hepatic failure after extended hepatectomy We reviewed the indications, scope and applicability of PVE/PVL in treatment of primary and secondary liver tumours. A thorough PubMED, Embase, Ovid and Cochrane database search was carried out for all original articles with 30 patients or more undergoing either PVE and any patient series with PVL, irrespective of number with outcome measure in at least one of the following parameters: FLR volume change, complications, length of stay, time to surgery, proportion resectable and survival data. PVE can be performed with a technical success in 98.9 % (95 % confidence interval 97–100) patients, with a mean morbidity of 3.13 % (95 % CI 1.21–5.04) and a median in-hospital stay of 2.1 (range 1–4) days (very few papers had data on length of stay following PVE). The mean increase in volume of the FLR following PVE was 39.75 % (95 % CI 30.8–48.6) facilitating extended liver resection after a mean of 37.13 days (95 % CI 28.51–45.74) with a resectability rate of 76.88 % (95 % CI 70.91–82.84). Morbidity and mortality following such extended liver resections after PVE is 26.58 % (95 % CI 19.20–33.95) and 2.59 % (95 % CI 1.34–3.83) respectively with an in-patient stay of 13.57 days (95 % CI 9.8–17.37). However following post-PVE liver hypertrophy 6.29 % (95 % CI 2.24–10.34) patients still have post-resection liver failure and up to 14.2 % (95 % CI −8.7 to 37) may have positive resection margins. Up to 4.80 % (95 % CI 2.07–7.52) have failure of hypertrophy after PVE and 17.46 % (95 % CI 11.89–23.02) may have disease progression during the interim awaiting hypertrophy and subsequent resection. PVL has a greater morbidity and duration of stay of 5.72 % (95 % CI 0–15.28) and 10.16 days (95 % CI 6.63–13.69) respectively; as compared to PVE. Duration to surgery following PVL was greater at 53.6 days (95 % CI 32.14–75.05). PVL induced FLR hypertrophy by a mean of 64.65 % (95 % CI 0–136.12) giving a resectability rate of 63.68 % (95 % CI 56.82–70.54). PVL failed to produce enough liver hypertrophy in 7.4 % of patients (95 % CI 0–16.12). Progression of disease following PVL was 29.29 (95%CI 15.69–42.88). PVE facilitates an extended hepatectomy in patients with limited or inadequate FLR, with good short and long-term outcomes. Patients need to be adequately counselled and consented for PVE and EH in light of these data. PVL would promote hypertrophy as well, but clearly PVE has advantages as compared to PVL on account of its inherent “minimally invasive” nature, fewer complications, length of stay and its feasibility to have shorter times to surgery.

Related papers:

title: Extension of surgical indications for hepatocellular carcinoma by portal vein embolization
abstract: We studied, clinically and experimentally, hypertrophy of the part of the liver not embolized after portal vein embolization (PVE). The subjects of the clinical study were 29 patients with hepatocellular carcinoma (HCC) who underwent embolization of the right first portal branch; 19 patients had cirrhosis, and 10 did not. The volume of the liver was calculated from computed tomograms obtained before PVE and 2 weeks after. In all patients, the volume of the nonembolized (left) lobe increased significantly. For the experimental study, we used male Wistar rats. Normal rats were untreated, and in the other rats cirrhosis was induced with carbon tetrachloride. The portal branch that supplies 70% of the total volume of the liver was embolized. The rats underwent one of four procedures: 70% PVE, 70% portal vein ligation, 70% hepatectomy, or laparotomy only. Rats were killed at different times after surgery, and the livers were removed and weighed. The mitotic index and DNA synthesis were measured in the nonembolized lobe (PVE group), in the lobe not supplied by the ligated branch (ligation group), or in the remaining liver (hepatectomy group). The liver weight, mitotic index, and DNA synthesis were high in the PVE, ligation, and hepatectomy groups for both normal rats and rats with cirrhosis. PVE caused cell proliferation and hypertrophy in the nonembolized part of the liver in the normal rats and even in those with cirrhosis. We concluded that PVE can extend the surgical indications for patients with HCC and underlying cirrhosis.RésuméUne étude clinique et expérimentale de l'hypertrophie du foie controlatéral a été réalisée chez les patients ayant eu une embolisation portale sélective (EP), Dans l'étude clinique, parmi les 29 patients ayant un carcinome hépatocellulaire (CHC) et ayant eu une embolisation de la droit première branche porte, 19 avaient une cirrhose, 10 n'en avaient pas. Le volume du foie a été déterminé avant et 2 semaines après EP par tomodensitométrie. Chez tous les patients, le volume du lobe hépatique non embolisé (lobe gauche) a augmenté de volume de faÇon significative. Dans l'étude expérimentale, on a induit une cirrhose par ingestion de tétrachlorure de carbone chez des rats Wistar. La branche porte correspondant à 70% du volume total du foie a été embolisée. Quatre types d'interventions ont été réalisées: EP de 70% du volume hépatique, ligature de 70% du territoire hépatique, hépatectomie de 70%, ou laparotomie exploratrice. Les rats ont été sacrifiés 1 à 14 jours après l'intervention. Le poids hépatique, l'index de mitoses, et la syntèse en ADN étaient élevés chez les rats avec ou sans cirrhose. L'EP était associée à une prolifération cellulaire et une hypertrophie du lobe non embolisé chez les rats normaux ou cirrhotiques. On conclut que l'EP peut étendre les indications de résection chirurgicale chez le patient ayant un CHC associé à une cirrhose.ResumenHemos estudiado la hipertrofia de la parte del hígado no embolizado después de embolización venosa portal (EVP) desde el aspecto clínico como experimental. La población del estudio estuvo constituído por 29 pacientes con carcinoma hepatocelular (CHC) sometidos a embolización de la primera derecha rama de la vena porta; 19 tenían cirrosis y 10 no eran cirróticos. El volumen del hígado fue calculado a partir de tomogramas computadorizados tornados antes de la EVP y dos semanas después. En todos los pacientes el volÚmen del lóbulo no embolizado aumentó en forma significativa. Se utilizaron ratas Wistar machos para el estudio experimental. Las ratas normales no recibieron tratamiento, y en las otras se indujo cirrosis con tetracloruro de carbono. La rama portal que irriga el 70% del volumen hepático total fue embolizada. Las ratas fueron sometidas a uno de cuatro procedimientos: 70% EVP, 70% ligadura de la vena portal, 70% hepatectomia o laparotomía simple; los animales fueron sacrificados a diferentes intervalos luego de la cirugía y los hígados removidos y pesados. Se determinaron el indice mitótico y la síntesis de DNA en el lóbulo no embolizado (grupo EVP), en el lóbulo no irrigado por la rama portal ligada (grupo ligadura) o en el hígado remanente (grupo hepatectomía). Tanto el peso del hígado como el indice mitótico y la síntesis de DNA aparecieron elevados en los grupos EVP, ligadura y hepatectomia tanto en ratas normales como en las cirróticas. La EVP causó proliferación celular e hipertrofia en la parte no embolizada del hígado en las ratas normales y aÚn en las ratas con cirrosis. Por consiguiente, la EVP amplifica las indicaciones quirÚrgicas en pacientes con CHC y cirrosis subyacente.

title: Improving Resectability of Hepatic Colorectal Metastases: Expert Consensus Statement
abstract: Although only10% 20% of patients with hepatic colorectal metas-tases are eligible for resection, the absolute number ofpatients amenable to resection is large and is growingwith better imaging, better surgery, and improve-ments in systemic therapies to reduce the risk of bothintrahepatic and extrahepatic recurrences.

title: Present status and future perspectives of preoperative portal vein embolization.
abstract: Portal vein embolization (PVE) has been gaining increasing acceptance before major hepatectomy. This review presents the application, outcome, and recent developments of PVE.



After a systematic search of "portal vein embolization" in PubMed, we reviewed and retrieved articles written in English related to PVE. There were no other criteria for exclusion of published information pertaining to this topic.



Hypertrophy of future liver remnants with PVE in patients with hepatobiliary malignancy results in fewer complications and shorter hospital stays after major hepatectomy, and add to the pool of candidates for surgical treatment. Some new techniques, such as sequential hepatic artery-portal vein embolization and PVE with stem cell administration, have showed a promising clinical future.



PVE has achieved significant improvement in the outcome of major hepatectomy, and has enlarged the candidate pool of liver resection as well. Future study is needed to identify the precise mechanism of liver regeneration after PVE.

title: Resection of nonresectable liver metastases from colorectal cancer after percutaneous portal vein embolization.
abstract: To assess the influence of preoperative portal vein embolization (PVE) on the long-term outcome of liver resection for colorectal metastases.



Preoperative PVE of the liver induces hypertrophy of the remnant liver and increases the safety of hepatectomy.



Thirty patients underwent preoperative PVE and 88 patients did not before resection of four or more liver segments. PVE was performed when the estimated rate of remnant functional liver parenchyma (ERRFLP) assessed by CT scan volumetry was less than 40%.



PVE was feasible in all patients. There were no deaths. The complication rate was 3%. The post-PVE ERRFLP was significantly increased compared with the pre-PVE value. Liver resection was performed after PVE in 19 patients (63%), with surgical death and complication rates of 4% and 7% respectively. PVE increased the number of resections of more than four segments by 19% (17/88). Actuarial survival rates after hepatectomy with or without previous PVE were comparable: 81%, 67%, and 40% versus 88%, 61%, and 38% at 1, 3, and 5 years respectively.



PVE allows more patients with previously unresectable liver tumors to benefit from resection. Long-term survival is comparable to that after resection without PVE.

title: Postoperative liver failure after major hepatic resection for hepatocellular carcinoma in the modern era with special reference to remnant liver volume.
abstract: Postoperative liver failure is a life-threatening complication after hepatic resection. Because of recent advances in liver surgery technique and a more stringent patient selection, mortality after hepatic resection has steadily decreased, but its incidence still ranges from 10% to 20%. The factors linked to postoperative liver failure in major hepatic resection in the modern era should be reevaluated.



Of 80 patients with viral markers (hepatitis C viral antibody or hepatitis B surface antigen) who underwent major hepatic resections (no less than bisegmentectomies) for hepatocellular carcinoma between 1990 and 1996, 7 patients (8.8%) died of postoperative liver failure within 6 months after hepatectomy. The cause of liver failure was analyzed based on both the preoperative data and the intraoperative findings. In addition, since all the patients who died of liver failure underwent a right hepatic lobectomy, a further data analysis was also done in 47 patients who underwent a right lobectomy of the liver. A volumetric analysis by CT was then done to evaluate the remnant liver volume.



Between the patients with liver failure and those without liver failure who underwent a right lobectomy, there were no significant differences in preoperative data or intraoperative findings. Volumetric analysis revealed that the remnant liver volume of patients who died of liver failure was significantly smaller than that of patients who lived (p = 0.008). The incidence of liver failure in patients with a remnant liver volume of less than 250 mL/m2 was 7 of 20 (38%), while it was 0 of 27 in patients with a liver volume of no less than 250 mL/m2 (p = 0.0012). The only significant risk factor for liver failure in patients with a remnant liver volume of less than 250 mL/m2 was diabetes mellitus (p = 0.0072).



The expected remnant liver volume appears to be a good predictor for liver failure in patients who undergo a right lobectomy of the liver. In patients with diabetes mellitus and an expected remnant liver volume of less than 250 mL/m2, a major hepatectomy should be avoided. Careful patient selection based on volumetric analysis in major hepatectomy cases could help prevent the occurrence of postoperative liver failure.

title: Two Hundred Forty Consecutive Portal Vein Embolizations Before Extended Hepatectomy for Biliary Cancer: Surgical Outcome and Long-term Follow-Up
abstract: To assess clinical benefit of portal vein embolization (PVE) before extended, complex hepatectomy for biliary cancer. Many investigators have addressed clinical utility of PVE before simple hepatectomy for metastatic liver cancer or hepatocellular carcinoma, but few have reported PVE before hepatectomy for biliary cancer due to the limited number of surgical cases. This study involved 240 consecutive patients with biliary cancer (150 cholangiocarcinomas and 90 gallbladder cancers) who underwent PVE before an extended hepatectomy (right or left trisectionectomy or right hepatectomy). All PVEs were performed by the “ipsilateral approach” 2 to 3 weeks before surgery. Hepatic volume and function changes after PVE were analyzed, and the outcome also was reviewed. There were no procedure-related complications requiring blood transfusion or interventions. Of the 240 patients, 47 (19.6%) did not undergo subsequent hepatectomy. The incidence of unresectability was higher in gallbladder cancer than in cholangiocarcinoma (32.2% versus 12.0%, P < 0.005). The remaining 193 patients (132 cholangiocarcinomas and 61 gallbladder cancers) underwent hepatectomy with resection of the caudate lobe and extrahepatic bile duct (n = 187), pancreatoduodenectomy (n = 42), and/or portal vein resection (n = 63). Seventeen (8.8%) patients died of postoperative complications: mortality was higher in gallbladder cancer than in cholangiocarcinoma (18.0% versus 4.5%, P < 0.05); and it was also higher in patients whose indocyanine green clearance (KICG) of the future liver remnant after PVE was <0.05 than those whose index was ≥0.05 (28.6% versus 5.5%, P < 0.001). The 3- and 5-year survival after hepatectomy was 41.7% and 26.8% in cholangiocarcinoma and 25.3% and 17.1% in gallbladder cancer, respectively (P = 0.011). In 136 other patients with cholangiocarcinoma who underwent a less than 50% resection of the liver without PVE, a mortality of 3.7% and a 5-year survival of 27.6% were observed, which was similar to the 132 patients with cholangiocarcinoma who underwent extended hepatectomy after PVE. PVE has the potential benefit for patients with advanced biliary cancer who are to undergo extended, complex hepatectomy. Along with the use of PVE, further improvements in surgical techniques and refinements in perioperative management are necessary to make difficult hepatobiliary resections safer.

title: Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer.
abstract: The epidermal growth factor receptor (EGFR), which participates in signaling pathways that are deregulated in cancer cells, commonly appears on colorectal-cancer cells. Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We compared the efficacy of cetuximab in combination with irinotecan with that of cetuximab alone in metastatic colorectal cancer that was refractory to treatment with irinotecan.



We randomly assigned 329 patients whose disease had progressed during or within three months after treatment with an irinotecan-based regimen to receive either cetuximab and irinotecan (at the same dose and schedule as in a prestudy regimen [218 patients]) or cetuximab monotherapy (111 patients). In cases of disease progression, the addition of irinotecan to cetuximab monotherapy was permitted. The patients were evaluated radiologically for tumor response and were also evaluated for the time to tumor progression, survival, and side effects of treatment.



The rate of response in the combination-therapy group was significantly higher than that in the monotherapy group (22.9 percent [95 percent confidence interval, 17.5 to 29.1 percent] vs. 10.8 percent [95 percent confidence interval, 5.7 to 18.1 percent], P=0.007). The median time to progression was significantly greater in the combination-therapy group (4.1 vs. 1.5 months, P<0.001 by the log-rank test). The median survival time was 8.6 months in the combination-therapy group and 6.9 months in the monotherapy group (P=0.48). Toxic effects were more frequent in the combination-therapy group, but their severity and incidence were similar to those that would be expected with irinotecan alone.



Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with irinotecan-refractory colorectal cancer.

title: Management of hepatic metastasis from colorectal cancers: an update.
abstract: Approximately 50%-60% of patients with colorectal cancers will develop liver lesions in their life span. Despite the potential of surgical resection to provide long-term survival in this subset of patients, only 15%-20% are found to be resectable. The introduction of new neoadjuvant chemotherapeutic agents and the expanding criteria of resection have enhanced the overall 5-year survival from 30% to 60% in the past decade. The use of technical innovations such as staged resection; portal vein embolization, and repeat resection have allowed higher resection rates in patients with bilobar disease. Extrahepatic primary and liver-exclusive recurrent disease no longer represent an absolute contraindication to resection. The role of regional therapy using hepatic arterial infusion is being redefined for liver-exclusive unresectable disease. Adjuvant chemotherapy in combination with regional therapies is being looked at from fresh perspectives. Ablative approaches have gained a firm role both as an adjunct to surgical resection and in the management of patients who are not surgical candidates. Overall, the management of hepatic metastasis from colorectal cancers requires a multimodal approach.

title: Should hepatic resections be performed at high-volume referral centers?
abstract: Recent studies have demonstrated the relationship between clinical outcomes of complex surgical procedures and provider volume. Hepatic resection is one such high-risk surgical procedure. The aim of this analysis was to determine whether mortality and cost of performing hepatic resection are related to surgical volume while also examining outcomes by extent of resection and diagnosis, variables seen with this procedure. Maryland discharge data were used to study surgical volume, length of stay, charges, and mortality for 606 liver resections performed at all acute-care hospitals between January 1990 and June 1996. One high-volume provider accounted for 43.6% of discharges, averaging 40.6 cases per year. In comparison, the remainder of resections were performed at 35 other hospitals, averaging 1.5 cases per year. Data were stratified into these high- and low-volume groups, and adjusted outcomes were compared. The mortality rate for all procedures in the low-volume group was 7.9% compared to 1.5% for the high-volume provider (P <0.01, relative risk = 5.2). No overall differences were observed between low- and high-volume providers in total hospital charges. When analyzing by procedure type and diagnosis, lower mortality was seen in the high-volume center for both minor and major resections, as well as resections for metastatic disease. It was concluded that hepatic resection can be performed more safely and at comparable cost at high-volume referral centers.

title: Extended hepatic resection: a 6-year retrospective study of risk factors for perioperative mortality.
abstract: Extended hepatic resection (more than four liver segments) is a major operative procedure that is associated with significant risk. The purpose of this study was to assess the impact of perioperative variables on in-hospital mortality after extended hepatectomy.



Consecutive patients who underwent extended hepatic resection were studied. The prognostic value of 29 perioperative variables was evaluated using in-hospital mortality as the endpoint. For each variable, the odds ratio (95% confidence interval) for in-hospital mortality was calculated. Those variables with a lower confidence limit > 1 were considered important risk factors. The population was stratified into categories of patients having the same number of risk factors, and mortality was estimated for each group. These data were used to develop a risk assessment algorithm.



There were 14 deaths (6%) in 226 patients. Three preoperative variables (cholangitis, creatinine > 1.3 mg/dL, and total bilirubin > 6 mg/dL) and two operative variables (blood loss > 3 L and vena caval resection) appear to be important factors for in-hospital mortality. The mortality associated with the presence of any two of the five factors was 100% (5 of 5), and the mortality associated with the absence of these factors was 3% (6 of 191).



Perioperative evaluation of patients undergoing extended hepatic resection should include the quantitation of mortality risk factors. The combination of any two factors among preoperative cholangitis, elevated serum creatinine, elevated serum bilirubin, high operative blood loss, and vena cava resection may carry a high mortality risk. These results require prospective validation.

title: Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases
abstract: Extrahepatic disease has always been considered an absolute contraindication to hepatectomy for liver metastases. The present study reports the long‐term outcome and prognostic factors of patients undergoing resection of extrahepatic disease simultaneously with hepatectomy for liver metastases.

title: A Two-Stage Hepatectomy Procedure Combined With Portal Vein Embolization to Achieve Curative Resection for Initially Unresectable Multiple and Bilobar Colorectal Liver Metastases
abstract: To assess outcome after a 2-stage hepatectomy procedure (TSHP) combined with portal vein embolization (PVE) in the treatment of patients with unresectable multiple and bilobar colorectal liver metastases (MBCLM). Patients with MBCLM are often considered for palliative chemotherapy only, due to too small future remnant liver (FRL). Recently, right hepatectomy with simultaneous left liver wedge resections after previous right PVE has been reported in a curative intent. However, the growth of metastatic nodules in FRL after PVE can be more rapid than that of the nontumoral remnant hepatic parenchyma. Therefore, metastases located in the FRL should be ideally resected before PVE. Then, a right (or extended right) hepatectomy can be safely performed during a second-stage hepatectomy. Therefore, we analyzed our experience with the use of TSHP combined with PVE in treatment of MBCLM. Between December 1996 and April 2003, 33 patients with unresectable MBCLM were selected for a TSHP. A right or an extended right hepatectomy was planned after treatment of left FRL metastases to achieve a curative resection. The first-stage hepatectomy consisted in a clearance of the left hemiliver by resection or radiofrequency destruction of metastases of the left FRL. Subsequently, a right PVE was performed to induce atrophy of the right hemiliver and hypertrophy of the left hemiliver. Finally, a second-stage hepatectomy was planned to resect the right liver metastases. There was no operative mortality. Post-PVE morbidity was 18.1%; postoperative morbidity was 15.1% and 56.0% after first- and second-stage hepatectomy, respectively. TSHP could be achieved in 25 of 33 patients (75.7%). The 1- and 3-year survival rates were 70.0% and 54.4%, respectively, in the 25 patients in whom the TSHP was completed. In selected patients with initially unresectable MBCLM, a TSHP combined with PVE can be achieved safely with long-term survival similar to that observed in patients with initially resectable liver metastases.

title: Late results justify resection for multiple hepatic metastases from colorectal cancer
abstract: Whilst hepatic resection is accepted for single colorectal metastases, the role of surgery for multiple deposits is less certain. This study reports results of a programme of aggressive resection of hepatic metastases.

title: Combined Portal Vein Embolization and Neoadjuvant Chemotherapy As a Treatment Strategy for Resectable Hepatic Colorectal Metastases
abstract: The objectives of this study are 1) to determine whether the future liver remnant will grow after portal vein embolization (PVE) in patients with colon cancer on concurrent chemotherapy and 2) to determine whether recovery after extended hepatectomy is improved after PVE. Neoadjuvant chemotherapy followed by hepatic resection is an increasingly used therapeutic strategy for curative treatment for colorectal metastases. However, such chemotherapy may result in steatosis, liver damage, and compromised liver regeneration and recovery. This study aims to determine whether PVE can be used during neoadjuvant therapy to enhance growth of future residual liver and to improve postoperative recovery. From September 1999 to September 2004, 100 patients with colorectal metastases to the liver were subjected to PVE as preparation for extended hepatic resection, 43 of whom were embolized during neoadjuvant chemotherapy. Liver growth was examined by computed tomography volumetric analysis. Clinical outcomes of the 71 patients subsequently resected were compared with 100 consecutive patients subjected to extended resection without PVE (controls). After a median wait of 30 ± 2 days after PVE, patients on neoadjuvant chemotherapy experienced a median contralateral (nonembolized) liver growth of 22% ± 3% compared with 26% ± 3% for those without chemotherapy (P = NS). The number of patients with <5% growth was also similar: 4 of 43 versus 6 of 57 (P = NS). Comparison of patients resected after PVE to a simultaneous cohort of 100 consecutive patients subjected to extended resection without prior PVE demonstrated a lower fresh frozen plasma requirement (P = 0.01), a lower peak bilirubin (P = 0.002), and a shorter length of stay (P = 0.03). Mortality was similar (0% vs. 2%). Liver growth occurs after PVE even when cytotoxic chemotherapy is administered. No major complications occurred with PVE. Patients requiring major hepatic resection should be considered for PVE during neoadjuvant chemotherapy to improve subsequent recovery after resection.

title: Rescue Surgery for Unresectable Colorectal Liver Metastases Downstaged by Chemotherapy: A Model to Predict Long-term Survival
abstract: To evaluate the long-term survival of patients resected for primarily unresectable colorectal liver metastases (CRLM) downstaged by systemic chemotherapy and to use prognostic factors of outcome for a model predictive of survival on a preoperative setting. Surgery of primarily unresectable CRLM after downstaging chemotherapy is still questioned, and prognostic factors of outcome are lacking. From a consecutive series of 1439 patients with CRLM managed in a single institution during an 11-year period (1988–1999), 1104 (77%) initially unresectable (NR) patients were treated by chemotherapy and 335 (23%) resectable were treated by primary liver resection. Chemotherapy mainly consisted of 5-fluorouracil and leucovorin combined to oxaliplatin (70%), irinotecan (7%), or both (4%) given as chronomodulated infusion (87%). NR patients were routinely reassessed every 4 courses. Surgery was reconsidered every time a documented response to chemotherapy was observed. Among 1104 NR patients, 138 “good responders” (12.5%) underwent secondary hepatic resection after an average of 10 courses of chemotherapy. At time of diagnosis, mean number of metastases was 4.4 (1–14) and mean maximum size was 5.2 cm (1–25). Extrahepatic tumor was present in 52 patients (38%). Multinodularity or extrahepatic tumor was the main cause of initial unresectability. All factors likely to be predictive of survival after liver resection were evaluated by uni- and multivariate analysis. Estimation of survival was adjusted on risk factors available preoperatively. Seventy-five percent of procedures were major hepatectomies (≥3 segments) and 93% were potentially curative. Liver surgery was combined to portal embolization, to ablative treatment, or to a second-stage hepatectomy in 42 patients (30%) and to resection of extrahepatic tumor in 41 patients (30%). Operative mortality within 2 months was 0.7%, and postoperative morbidity was 28%. After a mean follow-up of 48.7 months, 111 of the 138 patients (80%) developed tumor recurrence, 40 of which were hepatic (29%), 12 extrahepatic (9%), and 59 both hepatic and extrahepatic (43%). Recurrence was treated in 52 patients by repeat hepatectomy (71 procedures) and in 42 patients by extrahepatic resection (77 procedures). Survival was 33% and 23% at 5 and 10 years with a disease-free survival of 22% and 17%, respectively. It was decreased as compared with that of patients primarily resected within the same period (48% and 30% respectively, P = 0.01). At the last follow-up, 99 patients had died (72%) and 39 (28%) were alive; 25 were disease free (18%) and 14 had recurrence (10%). At multivariate analysis, 4 preoperative factors were independently associated to decreased survival: rectal primary, ≥3 metastases, maximum tumor size >10 cm, and CA 19–9 >100 UI/L. Mean adjusted 5-year survival according to the presence of 0, 1, 2, 3, or 4 factors was 59%, 30%, 7%, 0%, and 0%. Modern chemotherapy allows 12.5% of patients with unresectable CRLM to be rescued by liver surgery. Despite a high rate of recurrence, 5-year survival is 33% overall, with a wide use of repeat hepatectomies and extrahepatic resections. Four preoperative risk factors could select the patients most likely to benefit from this strategy.

title: Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report.
abstract: Extensive liver resection for hilar bile duct carcinoma with jaundice has high morbidity and mortality rates because of postoperative liver failure. To minimize postoperative liver dysfunction, a portal venous branch was embolized before surgery to induce atrophy of the lobe to be resected and hypertrophy of the contralateral lobe in 14 patients with hilar bile duct carcinoma. Bile was drained before surgery in 11 patients with jaundice. Portal embolization did not produce major side effects, and moderate increases of serum transaminase activity or bilirubin returned to baseline values within 1 week. Hepatectomy with bile duct resection and lymphadenectomy was performed 6 to 41 days after embolization, at which time the embolized lobe was atrophied in 12 of the patients. Extended right or left lobectomy or left trisegmentectomy (10, 3, and 1 cases, respectively) with biliointestinal reconstruction was performed. One patient with jaundice and suppurative cholangitis died 30 days after hepatectomy. Another patient died 3 months after surgery of aggravated hepatitis. After surgery, no bile leakage occurred and hyperbilirubinemia was usually moderate and reversible.

title: Preoperative portal vein embolization for hepatocellular carcinoma
abstract: As a countermeasure to portal tumor thrombi, which are a serious danger in liver cancer, we did portal vein embolization (PVE) during percutaneous transhepatic portography. Our 21 patients later underwent hepatic resection. After PVE, portal pressure increased and there was slight liver function damage, but this procedure was safer than transarterial embolization (TAE). We examined the pathologic specimens to view the state of occlusion achieved and also for histological findings, and found that Lipiodol ® mixed with fibrin was most effective. PVE done before hepatic resection strengthened the anticancer effect of TAE, prevented intrahepatic metastases, and caused permanent hypertrophy of the liver that may be useful as a kind of preparation for surgery.RésuméPour prévenir les dangers inhérents à la thrombose tumorale portale qui représente un danger sérieux en cas de cancer du foie, les auteurs procèdent à l'embolisation veineuse portale au cours de la portographie percutanée transhépatique. Les 21 malades traités par cette méthode subirent ensuite une résection hépatique. Après l'embolisation portale veineuse la pression portale augmente et les fonctions hépatiques sont légèrement altérées mais la méthode est moins dangereuse que l'embolisation artérielle. Les spécimens prélevés ont été examinés pour juger de l'efficacité de l'obstruction veineuse et aussi pour apprécier l'état histologique. Il a été constaté que l'association Lipiodol ®-fibrine pour réaliser l'embolisation veineuse était l'agent embolisant le plus efficace. La méthode pratiquée avant la résection hépatique dépasse l'effet anticancéreux de l'embolisation artérielle, prévient la dissémination des métastases hépatiques et provoque l'hypertrophie du foie restant fait qui peut être considéré comme utile avant d'avoir recours à l'exérèse du parenchyme hépatique.ResumenEn el Japón en años recientes se diagnostica con mayor frecuencia la presencia de pequeños carcinomas hepatocelulares. Sinembargo pequeños tumores comunmente dan lugar a trombos tumorales en la vena porta, complicación que empeora el pronóstico. Aún la embolización transarterial (ETA), que es efectiva contra el cáncer hepático, tiene casi ningún efecto contra los trombos tumorales. Como una medida contraria ante los trombos tumorales de la vena porta, los cuales significan tan alto riesgo en el cáncer del hígado, nos propusimos realizar embolización de la vena porta (EVP) en el curso de la portografía percutánea transhepática. Nuestros 21 pacientes fueron posteriormente sometidos a resección hepática. Después de EVP, la presión en la vena porta ascendió y se observó leve alteración de la función hepática, pero el procedimiento résultó más seguro que la ETA. Se hizo exámen de los especímenes patológicos para determinar el grado de oclusión obtenido y los hallazgos histológicos y se encontró que el Lipiodol ® mezclado con fibrina fue el material más efectivo. La EVP realizada con anterioridad a la resección hepática incrementa el efecto anticancerígeno de la ETA, previene el desarrollo de metástasis intrahepáticas y causa hipertrofia del hígado, o sea regeneración del hígado del tipo que se produciría con la resección, efecto que puede ser beneficioso como preparación del paciente para cirugía.

title: Application of preoperative portal vein embolization before major hepatic resection in patients with normal or abnormal liver parenchyma.
abstract: Clinical parameters influencing the effect of preoperative portal vein embolization (PVE) in hypertrophying the nonembolized lobe of patients with either normal or abnormal liver parenchyma and its effect upon portal pressure were examined to identify the patient population for whom this approach is most suited.



The study population included 43 patients undergoing major hepatectomy after PVE. Patients were divided into 2 groups according to their liver parenchyma: 17 patients with normal liver parenchyma (N group) and 26 patients with damaged liver parenchyma due to viral hepatitis (D group). We calculated the correlation between volumetric increases in the nonembolized (left) lobe after PVE (hypertrophic ratio = post-PVE left lobe volume/pre-PVE left lobe volume) using computed tomography volumetry before and 2 weeks after PVE. Clinical parameters also were examined to identify those parameters modifying the hypertrophic ratio in each group, and changes in portal pressure by PVE and the subsequent hepatectomy were recorded. Finally, by comparing patients with or without postoperative liver failure after hepatectomy, the influence of the hypertrophic ratio and portal pressure on the outcome of subsequent hepatectomy was examined.



The hypertrophic ratio was 1.34 +/- 0.23 in the N group, and 1.25 +/- 0.21 in the D group. This difference was not significant. Multiple regression analysis revealed that the parenchymal volumetric rate of the right lobe (PVR) in the D group and both PVR and prothrombin time in the N group were independent parameters predicting the hypertrophic ratio. The portal pressure increased immediately after PVE and was similar in both groups to levels after hepatectomy. Six patients in the D group experienced postoperative liver dysfunction. In 5 of these 6 patients, the hypertrophic ratio was below 1.2, and the portal pressure was higher than that in patients without liver dysfunction.



PVE induces hypertrophy of the nonembolized lobe of both abnormal and normal liver parenchyma, and the effect was predictable. Postoperative liver failure appeared to be more severe in patients having a lower hypertrophic ratio and higher portal pressure in abnormal liver parenchyma, however. PVE also may have diagnostic use in predicting portal pressure after hepatectomy, which may be associated with surgical outcome.

title: Preoperative percutaneous portal vein embolization: evaluation of adverse events in 188 patients.
abstract: To retrospectively assess the frequency of adverse events related to percutaneous preoperative portal vein embolization (PPVE).



Institutional review board did not require its approval or patient informed consent for this study. The adverse events that occurred during PPVE or until planned hepatic surgery was performed or cancelled were retrospectively obtained from clinical, imaging, and laboratory data files in 188 patients (109 male and 79 female patients; mean age, 60 years; range, 16-78 years). Liver resection was planned for metastases (n = 137), hepatocarcinoma (n = 31), cholangiocarcinoma (n = 15), fibrolamellar hepatoma (n = 1), and benign disease (n = 4). PPVE was performed with a single-lumen 5-F catheter and a contralateral approach with n-butyl cyanoacrylate mixed with iodized oil as the main embolic agent. The rate of complications in patients with cirrhosis was compared with that in patients without cirrhosis by using the chi(2) test.



Adverse events occurred in 24 (12.8%) of 188 patients, including 12 complications and 12 incidental imaging findings. Complications included thrombosis of the portal vein feeding the future remnant liver (n = 1); migration of emboli in the portal vein feeding the future remnant liver, which necessitated angioplasty (n = 2); hemoperitoneum (n = 1); rupture of a metastasis in the gallbladder (n = 1); transitory hemobilia (n = 1); and transient liver failure (n = 6). Incidental findings were migration of small emboli in nontargeted portal branches (n = 10) and subcapsular hematoma (n = 2). Among the 187 patients in whom PPVE was technically successful, there was a significant difference (P < .001) between the occurrence of liver failure after PPVE in patients with cirrhosis (five of 30) and those without (one of 157). Sixteen liver resections were cancelled due to cancer progression (n = 12), insufficient hypertrophy of the nonembolized liver (n = 3), and complete portal thrombosis (n = 1).



PPVE is a safe adjuvant technique for hypertrophy of the initially insufficient liver reserve. Post-PPVE transient liver failure is more common in patients with cirrhosis than in those without cirrhosis.

title: Pre-hepatectomy portal vein embolization: single center experience.
abstract: To evaluate the feasibility and the effectiveness of portal vein embolization (PVE) as preoperative treatment in patients scheduled to undergo right hepatectomy, when the volume of the future remnant liver (FRL) appears to be insufficient to prevent the risk of post-surgical hepatic failure.



Thirty-one consecutive patients (19 men, 12 women; age range: 54-77 years; mean age: 66.2 years) with liver malignancy (7 hepatocellular carcinoma, 13 metastases, 9 cholangiocarcinoma, and 2 gallbladder carcinoma) were selected after clinical-radiological evaluation for PVE. After the embolization changes in volume of FRL, portal pressure, liver enzymes, and complications before and after hepatectomy were assessed.



PVE was successful in all patients without major complications. The mean volume of FRL, calculated before and 4 weeks after PVE, increased from 319.2 +/- 45.1 to 460.2 +/- 27.7 cm(3) (+44.2%) in the non-cirrhotic group and from 458.4 +/- 38.3 to 605.2 +/- 27 cm(3) (+32.1%) in the cirrhotic group. The FRL/TELV ratio increased by 9%.



In our experience, PVE resulted feasible, safe, with a very low rate of complications, and effective to induce liver regeneration before right hepatectomy in patients with liver malignancy.

title: Preoperative portal vein embolization: An audit of 84 patients
abstract: Preoperative portal vein embolization (PVE) was performed in 84 patients before extensive liver resection for various diseases. By the criteria of liver volumetric determination, some patients were candidates for PVE, whereas others were not, even though the same surgical procedure, such as extended right lobectomy (ERL), was scheduled. PVE using gelatin sponge powder induced hypertrophy in the nonembolized lobe (0%‐171%; median, 30%) and proportional atrophy in the embolized lobe in 2 weeks without eliciting any major inflammatory or necrotic reaction, as evidenced histologically and by the minimal elevations in the serum aspartate transaminase (AST) and alanine transaminase (ALT) values. Alterations in the total bilirubin level and prothrombin time were also insignificant and transient, indicating that hepatocyte functions were not impaired by PVE. Not all patients who undergo PVE proceed with the scheduled hepatic resection procedure, so it is a great advantage that gelatin sponge causes minimal damage compared with other embolizing materials such as cyanoacrylate and absolute ethanol, which have been reported to induce an inflammatory reaction or histological alteration. Our multiple regression analysis showed that three factors, diabetes mellitus, a high total bilirubin level at the time of PVE, and being male, each reduced the extent of hypertrophy in the nonembolized lobe (r2 = .30). By contrast, cholestasis appeared to accelerate the process of atrophy in the embolized lobe (r2 = .16). In conclusion, PVE by gelatin sponge powder is a safe and effective preoperative maneuver that induces hypertrophy of the section of the liver that will remain after partial hepatectomy

title: Preoperative portal vein embolization for extension of hepatectomy indications
abstract: To render hepatectomy feasible in patients with an initially deficient volume of the future remnant liver (FRL), we redistributed portal blood flow rich in hepatotrophic substances toward the FRL. Redistribution was achieved with preoperative portal vein embolization (POPE) feeding the future resected liver. POPE was performed in 31 patients, under fluoroscopic guidance, via a percutaneous access. POPE was well tolerated and surgery was practicable in 24 patients without severe postoperative liver failure. Seven operations were cancelled, but only one due to insufficient hypertrophy of the FRL. FRL volume values were 90 to 560 mL (mean 260 mL) before POPE and 160‐783 mL (mean 443 mL) after POPE, which represents a median increase of 79% ± 50%. Hypertrophy of the FRL was 90% ± 52% after 30 days with cyanoacrylate, 53% ± 6% after 43 days with Gelfoam, and 44% ± 30% after 35 days with coils. Slight shrinkage was obtained in the volume of the embolized liver, for which resection was planned. Overall survival was 2‐62 months (mean 26 months), disease‐free survival was 0‐60 months (mean 19 months), and 7 patients are disease‐free and alive 14 to 60 months (mean 43 months) after surgery. Although exclusively applicable in a limited subset of patients, POPE widens the possibilities of curative hepatectomies, because it induces sound hypertrophy of unembolized liver segments. Cyanoacrylate seems to ensure better and faster hypertrophy.

title: Preoperative contralateral portal vein embolization before major hepatic resection is a safe and efficient procedure: a large single institution experience.
abstract: The aim of this study was to report the results of preoperative contralateral portal vein embolization (PVE) performed in a single institution.



Between January 1997 and March 2006, 146 patients requiring a right or extended right hepatectomy for primary or secondary liver tumors underwent contralateral PVE when the future remnant liver volume (FRL) was less than 30% of total liver. Liver volumes and hepatic function were evaluated before and after PVE.



Contralateral PVE was performed successfully in 145 patients. In one patient, the catheterization of the left portal branch failed. Complications occurred in 14 patients (10%) including a transitory fever (n = 9), a parenchymal hematoma (n = 1), a mild hemoperitoneum (n = 1), a mesenterico-portal venous thrombosis (n = 1), a pulmonary embolism (n = 1) and a systemic sepsis (n = 1). The prothrombin ratio and the platelet count were significantly lower 3 days after PVE. Insufficient hypertrophy of the FRL was observed in 8 patients, malignant disease progression in 15, and both insufficient hypertrophy and disease progression in 4. The hypertrophy rate of the FRL 4 to 8 weeks after PVE was 47.7 +/- 31.9%. Pathological type of the liver tumor, cirrhosis, diabetes mellitus, and chemotherapy did not affect the volume of the left liver hypertrophy. However, the time required to achieve an adequate liver hypertrophy was significantly shorter in patients with normal liver. One-hundred and fourteen patients (78.6%) subsequently underwent hepatic resection.



The results suggest that contralateral PVE is a safe and efficient procedure inducing adequate hypertrophy of the FRL before major liver resection.

title: New possibilities for major liver surgery in patients with Klatskin tumors or primary hepatocellular carcinoma--an old problem revisited.
abstract: An impaired liver function secondary to liver disease is considered a contra-indication for extensive liver resection because of the risk of liver failure. Selective embolization of the portal branch corresponding to the part of the liver that is considered for resection, carried out three to four weeks before surgery, reportedly induced atrophy of the embolized part of the liver with hypertrophy of the nonembolized part. This policy showed satisfactory early results in 46 patients who had extended liver resection. One patient with severe cholangitis died in the first 30 days. Seven patients had minor complications, which responded well to conservative management (subphrenic abscesses 3, wound infections 3, pulmonary infection 1). Selective portal embolization was well tolerated and was associated with temporary mild side effects. Liver functions before and after embolization returned to pre-embolization values. The present results support the policy of selective portal embolization in patients with impaired liver function in whom extensive liver resection is necessary. Embolization is a promising ancillary preoperative alternative.

title: Preoperative Portal Vein Embolization and Surgical Resection in Patients with Hepatocellular Carcinoma and Small Future Liver Remnant Volume: Comparison with Transarterial Chemoembolization
abstract: BackgroundPreoperative portal vein embolization (PVE) increases the future liver remnant (FLR) volume, thus enabling surgical resection in patients with small FLR volume. It is unclear, however, if this approach can enhance survival in patients with hepatocellular carcinoma (HCC). We therefore compared the outcomes of preoperative PVE and surgical resection with transarterial chemoembolization (TACE).MethodsChanges in FLR volumes were analyzed in 32 HCC patients who underwent preoperative PVE and surgical resection. Long-term outcomes were compared with 64 TACE-treated patients matched for gender, Child-Turcotte-Pugh class, tumor size and number, serum alpha-fetoprotein levels, and UICC stage.ResultsIn the PVE group, the baseline ratio of FLR/total estimated liver volumes (TELV) was 27.6 ± 7.2%. Following PVE, FLR volume increased 34% (336.5 vs 449.4 mL, P < .001) and the ratio of FLR/TELV increased from 27.6 ± 7.2 to 36.9 ± 8.1% (P < .001). There was no mortality associated with PVE or surgical resection. The 5-year survival rate was significantly higher in the PVE group than in the TACE group (71.9% vs 45.6%, P = .03). Multivariate analysis showed that treatment modality was an independent predictive factor for survival (odds ratio 2.05, 95% confidence interval 1.01–4.16, P = .046).ConclusionsPreoperative PVE enables surgical resection in HCC patients with small FLR volume and improves patient survival compared with TACE.

title: Major Hepatectomy for Colorectal Metastases: Is Preoperative Portal Occlusion an Oncological Risk Factor?
abstract: BackgroundThis study investigates oncological risks and benefits of portal occlusion (PO) in major resection for colorectal liver metastases (CLM).MethodsBetween 1995 and 2004, 107 patients were scheduled for major hepatectomy for CLM. Of these, 53 patients were selected for PO due to insufficient future liver remnant (FLR), and 54 patients had straightforward hepatectomy. Associations of clinicopathologic factors with resectability, and outcome after PO were analyzed.Results21 of 53 patients (39.6%) after PO were unresectable. These patients had a significant smaller volume of the FLR than the 32 resected patients after PO (P = .029). In total, 17 patients (80.9%) did not undergo resection due to cancer progression. Among these, 11 patients (52.4%) exhibited either a progression of known metastases located in the occluded lobes, or new metastases in the nonoccluded portion of the liver. In another 4 individuals (19%), the decision against resection resulted from insufficient hypertrophy of the FLR. Following major hepatectomy, the 5-year survival was 43.66%. Although there was a significantly higher rate of extended hepatectomies versus formal hepatectomies (P < .001), more bilobar distributed metastases versus unilobar manifestations (P = .015), and a smaller resection margin (P = .01) in patients who had PO, no adverse effect on mortality, morbidity, recurrence and survival was observed.ConclusionUnresectability after PO is a major problem that warrants multidisciplinary improvements, and randomization to resection with or without PO remains ethically problematic. However, following adequate patient selection, PO may provide a significant survival benefit for patients with prior unresectable CLM.

title: Portal vein embolization before major hepatectomy and its effects on regeneration, resectability and outcome
abstract: This study evaluated the safety of portal vein embolization (PVE), its impact on future liver remnant (FLR) volume and regeneration, and subsequent effects on outcome after liver resection.

title: Portal vein ligation as an efficient method of increasing the future liver remnant volume in the surgical treatment of colorectal metastases.
abstract: To compare the volumetric increase of segments 2 and 3, segment 4, and the caudate lobe after portal vein ligation (PVL) and portal vein embolization (PVE). The small size of the remnant liver and chemotherapy-induced liver injury increase the risk of postoperative hepatic insufficiency after major hepatic resection for colorectal liver metastases. Portal vein ligation has been suggested to be less effective than embolization in inducing hypertrophy of the remnant liver.



We retrospectively reviewed 48 patients with colorectal liver metastases who underwent PVL (n = 17) or PVE (n = 31) at the Istituto per la Ricerca e la Cura del Cancro or the Institut Paoli-Calmette from March 1, 2000, through August 31, 2006.



To compare the volume increase of segments 2 and 3, segment 4, and of the caudate lobe in patients who have undergone PVL or PVE in preparation for a major hepatic resection.



There were no deaths related to PVE or PVL. Portal vein ligation was associated with resection of synchronous colorectal cancer in 16 patients. Resection of a liver metastasis in the remnant liver was performed in 11 patients. The median estimated baseline volume of segments 2 and 3 was 17.7% in the PVL group and 17.5% in the PVE group (P = .72). After PVL or PVE, it increased to 26.9% and 24.7%, respectively (P = .95), for volumetric increases of 43.1% and 53.4%, respectively (P = .39). The volumetric increases of segment 4 and the caudate lobe were similar.



Portal vein ligation is as effective as PVE in inducing hypertrophy of the remnant liver volume.

title: Impact of portal vein embolization on long‐term survival of patients with primarily unresectable colorectal liver metastases
abstract: Portal vein embolization (PVE) increases the resectability of initially unresectable colorectal liver metastases (CLM). This study evaluated long‐term survival in patients with CLM who underwent hepatectomy following PVE.

title: Role of portal vein embolization in liver surgery: single centre experience in sixty-two patients
abstract: The extent of liver resection is limited by the residual functional reserve of the liver (FLR). The introduction of portal vein embolization (PVE), with the rationale of inducing hypertrophy of the FLR has significantly reduced morbidity and in particular the impact of postoperative liver failure (PLF). The objective of the study is to evaluate the feasibility and effectiveness of PVE in patients candidates to liver resections with high risk of PLF. Between January 2006 and December 2009, 62 patients suffering from primary or metastatic liver tumour, underwent PVE at the Department of Surgery–Liver Unit HSR. CT assessment of hepatic volume was performed in each patient, prior and 4 weeks after the procedure. The outcome was evaluated in terms of feasibility of surgery, FLR growth [calculated as: (FLR after PVE − FLR pre PVE) × 100/FLR pre PVE], morbidity and mortality associated with PVE and surgery. Of the 62 patients undergoing PVE, 6 (9.7%) did not benefit from surgery: of these, 4 showed spread of disease in the FLR at CT control, while in the remaining 2 adequate hypertrophy was not reached. The average volume of the FLR at the time of the procedure and after 4 weeks was 437.03 cc (±172.54) and 615.15 cc (± 187.49), respectively, with an average increase of 50.3% (±30.31). During the postoperative period, only 2 patients (3.2%) showed mild and transient signs of the PLF. The technique of PVE allows to performing, in an effective and safe way, major liver resections in patients with high risk of PLF.

title: Preoperative portal vein embolization using an amplatzer vascular plug
abstract: The purpose was to evaluate the safety and efficacy of preoperative portal vein embolization (PVE) using an Amplatzer vascular plug (AVP). Forty-one patients who underwent PVE using gelatin sponge particles and the AVP were enrolled. The right portal branches were embolized using gelatin sponges (1–8 mm3) through a 5-F catheter, and the AVP was deployed at the first- or second-order right portal vein. Technical success and complications, recanalization, and changes of total estimated liver volumes (TELV), future liver remnant (FLR), and FLR/TELV were evaluated. Follow-up CT performed 6–43 days (median, 16 days) after PVE was used to evaluate volume parameters. PVE was technically successful in 40 of 41 patients. Major complications occurred in two patients, with one each having extensive portal vein thrombosis and liver abscess. Partial recanalization of the occluded portal vein was seen in one patient. The mean FLR volume (653 ± 174 ml vs. 532 ± 154 ml, p < 0.001) and mean FLR/TELV ratio (43 ± 8% vs 36 ± 7%, p < 0.001) were significantly higher after than before PVE. PVE using the AVP seems to be a relatively safe and effective technique for inducing hypertrophy of the FLR with minimal risk of recanalization.

title: Portal vein embolization vs. portal vein ligation for induction of hypertrophy of the future liver remnant
abstract: The objective of this study was to assess the efficacy of right portal vein embolization (PVE) vs. right portal vein ligation (PVL) for induction of hypertrophy of the left lateral liver lobe before extended right hepatectomy. Thirty-four patients with primary or secondary liver tumors and estimated remnant functional liver parenchyma of less than 0.5% of body weight underwent either right PVE (transcutaneous, n= 10; transileocolic, n =7) or right PVL (n=17). Liver volume was assessed by CT scan before occlusion of the right portal vein and prior to resection. There were no deaths. The morbidity rate in each group was 5.8% (PVE, 1 abscess; PVL, 1 bile leak). The increase in liver volume was significantly higher after PVE compared with PVL (188±81 ml vs. 123±58 ml) (P= 0.012). Postoperative hospital stay was significantly shorter after PVE in comparison to PVL (4±2.9 days vs. 8.1±5.1 days;P<0.01). Curative liver resection was performed in 10 of 17 patients after PVE and 11 of 17 patients after PVL. PVE and PVL were found to be feasible and safe methods of increasing the remnant functional liver volume and achieving resectability for extended liver tumors. PVE results in a significantly more efficient increase in liver volume and a shorter hospital stay.

title: Right Portal Vein Ligation is as Efficient as Portal Vein Embolization to Induce Hypertrophy of the Left Liver Remnant
abstract: BackgroundAim of this retrospective study was to compare induction of left liver hypertrophy after right portal vein ligation (PVL) and right portal vein embolization (PVE) before right hepatectomy for liver metastases.Materials and MethodsBetween 1998 and 2005, 18 patients underwent a PVE, whereas 17 patients underwent a PVL during a first stage laparotomy.ResultsThere was no complication related to PVE or PVL. After a similar interval time (7 ± 3 vs 8 ± 3 weeks), the increase of the left liver volume was similar between the two groups (35 ± 38 vs 38 ± 26%). After PVE and PVL, right hepatectomy was performed in 12 and 14 patients, respectively. Technical difficulties during the right hepatectomy were similar according to duration of procedure (6.4 ± 1 vs 6.7 ± 1 h, p = 0.7) and transfusion rates (33 vs 28%, p = 0.7). Mortality was nil in both groups, and morbidity rates were respectively 58% for the PVE group and 36% for the PVL group (p = 0.6).ConclusionRight PVL and PVE result in a comparable hypertrophy of the left liver. During the first laparotomy of a two-step liver resection, PVL can be efficiently and safely performed.

title: Feasibility of laparoscopic portal vein ligation prior to major hepatectomy.
abstract: Patients noted to have an inadequate future liver remnant on pre operative volumetric assessment are considered to be candidates for portal vein embolization (PVE). A subset of patients undergo laparoscopic intervention prior to PVE for staging purposes or to address the primary in Stage IV colon cancer. These patients usually undergo PVE as a subsequent additional procedure by the transhepatic route. The aim of this study was to assess the feasibility of portal vein ligation by the laparoscopic approach in suitable patients.



A retrospective review of a prospectively maintained database was performed to identify patients that underwent laparoscopic portal vein ligation (LPVL). The demographic, clinical, radiographic, operative and volumetric details were collected to determine the feasibility of portal vein ligation.



A total of nine patients underwent LPVL as part of a two stage procedure in preparation for subsequent major hepatectomy. With a median age of 67 yrs, the diagnoses included: colorectal metastasis (five patients), cholangiocarcinoma (three patients) and hepatocellular carcinoma (one patient). The ligation involved the right portal vein in all and was performed with silk ligature (seven patients) and clips (two patients). Volumetric data was available in six patients which showed a mean increase from 209.1 cc+/-97.76 to 495.83 cc+/-310.91 (increase by 181.5%) In two patients, inadequate hypertrophy mandated later embolization by percutaneous technique. Five patients underwent subsequent major hepatic resection as planned. The remaining four patients were noted to have progression of disease that precluded the planned procedure. There were no complications associated with LPVL.



LPVL is feasible and can be safely performed. In a select group of patients, it may be considered as an alternative to subsequent embolization and thereby potentially absolve the need for an additional procedure with its attendant complications.

title: Right portal vein ligation: a new planned two-step all-surgical approach for complete resection of primary gastrointestinal tumors with multiple bilateral liver metastases.
abstract: Although complete resection of liver metastases remains the only curative treatment for metastatic liver disease from colorectal and endocrine gastrointestinal (GI) tumors, only a small proportion of patients with liver metastases are candidates for potentially curative surgery. Among these, 4% to 21% are found to have unresectable disease because of multiplicity of the liver metastases, so a very small proportion of such patients can be eligible for complete resection. When the number and distribution of liver metastases create the need for extensive hepatic resection, the risk for postoperative liver failure and morbidity related to the small size of the remnant liver is increased. Additionally, substantial operative risk results from the combination of extensive hepatic resection with other major abdominal procedures at a single operation, such as extended hepatectomy with colorectal or pancreatic resections. On the other hand, minor hepatic surgery, such as left liver wedge resection, has been shown to be safe in combination with such extrahepatic procedures as those necessary to treat many GI primary tumors. So, multistep, multimodality therapies including surgery in several steps have been proposed and usually require resection of the primary tumor in one step, followed by extensive liver resection, with or without the use of percutaneous ablative therapy or systemic chemotherapy. Improved understanding of the benefits of liver regeneration has led to other approaches using intermediate steps between surgical procedures. In patients expected to have a small future liver remnant volume (FLR), most hepatic surgeons perform preoperative portal vein embolization (PVE), mainly to avoid postoperative liver failure and to decrease morbidity either after major hepatectomy in patients with injured liver parenchyma (such as that found in patients after extensive chemotherapy or in patients with chronic liver disease) or when major hepatectomy is associated to major abdominal procedures. But some investigators suggest that in patients with bilobar liver metastases from colorectal cancer, hypertrophy of the left liver induced by right PVE might accelerate the progression of left-sided disease and therefore caution against the reckless use of PVE in these cases. In order to use the benefits of diversion of portal flow to the FLR, to avoid the risk of progression of liver disease, and to minimize the risk and number of procedures necessary to treat patients with GI tumors with bilobar liver metastases, we developed a new planned two-step, totally surgical approach to clear all primary and metastatic disease. In the first step, the primary tumor and all left-sided liver metastases (Couinaud S1 to S4) are resected using straightforward resection techniques. Simultaneously, right portal vein ligation (RPVL) is performed to induce hypertrophy in the left lobe, which has been cleared of all detectable disease. Four to 8 weeks later, after hypertrophy of the diseasefree FLR, a second step consisting of a right or extended right hepatectomy is planned to completely clear the remaining right-sided liver metastases . No competing interests declared.

title: Right portal embolization before extended right hepatectomy using laparoscopic catheterization of the ileocolic vein: a prospective study.
abstract: Preoperative embolization of the right portal vein branch before extended right hepatectomy for hepatocellular carcinoma or hilar cholangiocarcinoma has been recommended for the prevention of postoperative liver failure. Percutaneous transhepatic insertion into the intrahepatic portal vein and insertion into the ileocolic vein at open laparotomy are used for inserting a catheter introducer into the portal vein. We devised a new technique for the laparoscopic insertion of a catheter introducer into the ileocolic vein and used it for right portal embolization in three patients. Measurement of hepatic volume by computed tomography 3 weeks after right portal embolization showed a 28.6 to 66.0% increase in the volume of the predicted remnant liver. This minimally invasive procedure has three advantages: reduction of postoperative pain, avoidance of hepatic injury, and the opportunity for a laparoscopic observation of the liver and the intra-abdominal organs before right portal embolization and hepatectomy.

title: Transjugular preoperative portal embolization (TJPE) a pilot study.
abstract: Because of our previous experience with transjugular intrahepatic portosystemic shunt, we decided to apply the transjugular approach to preoperative portal embolization. The aim of this pilot study was to determine the feasibility and the potential advantages and disadvantages of this new method.



Under ultrasound guidance the right or left portal branch was punctured from the right, median or left hepatic vein. Then, a catheter was placed near the portal bifurcation and used to perform right portal branch embolization with a mixture of Histoacryl and Lipiodol. Pre- and post-transjugular preoperative portal embolization duplex ultrasound and CT scan were performed to assess portal flow and liver tissue growth. Hospital stay, pain and hepatic enzymes were monitored.



Fifteen patients underwent a transjugular preoperative portal embolization without any serious complication. Mean of hospital stay was 3.3 +/- 0.6 days. (2-5 days). Portal embolization was successful in all cases; left portal branch velocity increased from 11.8 +/- 7.5 cm/s before, to 16.5 +/- 3.5 cm/s on day one, and 14.8 +/- 3.3 cm/s on day 28 after transjugular preoperative portal embolization; volume of non-embolized segments increased by 10% within the 4 weeks after transjugular preoperative portal embolization. Right hepatectomy was possible in 12 patients



This method is safe, painless, and can be proposed in cases of impossibility to perform the standard percutaneous transhepatic portal embolization (tumor interposition, impaired hemostasis).

title: Transhepatic portal vein embolization: anatomy, indications, and technical considerations.
abstract: Portal vein embolization (PVE) is increasingly being accepted as a useful procedure in the preoperative treatment of patients selected for major hepatic resection. PVE is performed via either the percutaneous transhepatic or the transileocolic route and is usually reserved for patients whose future liver remnants are too small to allow resection. It is a safe and effective method for inducing selective hepatic hypertrophy of the nondiseased portion of the liver and may thereby reduce complications and shorten hospital stays after resection. A thorough knowledge of hepatic segmentation and portal venous anatomy is essential before performing PVE. In addition, the indications and contraindications for PVE, the methods for assessing hepatic lobar hypertrophy, the means of determining optimal timing of resection, and the possible complications of PVE need to be fully understood before undertaking the procedure. Technique may vary among operators, and further research is necessary to determine the best embolic agents available and the expected rates of liver regeneration for PVE. Nevertheless, as hepatobiliary surgeons become more experienced at performing extended hepatic resections, PVE may be requested more frequently.

title: Standardized measurement of the future liver remnant prior to extended liver resection: methodology and clinical associations.
abstract: There is no agreement regarding the preoperative measurement of liver volumes and the minimal safe size of the liver remnant after extended hepatectomy.



In 20 patients with hepatobiliary malignancy and no underlying chronic liver disease, volumetric measurements of the liver remnant (segments 2 and 3 +/- 1) were obtained before extended right lobectomy (right trisegmentectomy). The ratios of future liver remnant to total liver volume were calculated by using a formula based on body surface area. In 12 patients, response to preoperative right trisectoral portal vein embolization was evaluated. In 15 patients who underwent the planned resection, preoperative volumes were correlated with biochemical and clinical outcome parameters.



The future liver remnants increased after portal vein embolization (26% versus 36%, P < .01). Smaller size liver remnants were associated with an increase in postoperative liver function tests (P < .05) and longer lengths of hospital stay (P < .02). Preliminary data indicates an increase in major complications for liver volumes < or = 25% (P = .02).



A simple method of measurement provides an assessment of the liver remnant before resection. It is useful in evaluating response to portal vein embolization and in predicating the outcome before extended liver resections.

title: Transhepatic ipsilateral right portal vein embolization extended to segment IV: improving hypertrophy and resection outcomes with spherical particles and coils.
abstract: To analyze outcomes after right portal vein embolization extended to segment IV (right PVE + IV) before extended right hepatectomy, including liver hypertrophy, resection rates, and complications after embolization and resection, and to assess differences in outcomes with two different particulate embolic agents.



Between 1998 and 2004, transhepatic ipsilateral right PVE + IV with particles and coils was performed in 44 patients with malignant hepatobiliary disease, including metastases (n = 24), biliary cancer (n = 14), and hepatocellular carcinoma (n = 6). Right PVE + IV was considered if the future liver remnant (FLR; segments II/III with or without I) was less than 25% of the total estimated liver volume (TELV). Tris-acryl microspheres (100-700 microm; n = 21) or polyvinyl alcohol (PVA) particles (355-1,000 microm; n = 23) were administered in a stepwise fashion. Smaller particles were used to occlude distal branches, followed by larger particles to occlude proximal branches until near-complete stasis. Coils were then placed in secondary portal branches. Computed tomographic volumetry was performed before and 3-4 weeks after right PVE + IV to assess FLR hypertrophy. Liver volumes and postembolization and postoperative outcomes were measured.



After right PVE + IV with PVA particles, FLR volume increased 45.5% +/- 40.9% and FLR/TELV ratio increased 6.9% +/- 5.6%. After right PVE + IV with tris-acryl microspheres, FLR volume increased 69.0% +/- 30.7% and FLR/TELV ratio increased 9.7% +/- 3.3%. Differences in FLR volume (P = .0011), FLR/TELV ratio (P = .027), and resection rates (P = .02) were statistically significant. Seventy-one percent of patients underwent extended right hepatectomy (86% after receiving tris-acryl microspheres, 57% after receiving PVA). Thirteen patients (29%) did not undergo resection (extrahepatic spread [n = 9], inadequate hypertrophy [n = 3], other reasons [n = 1]). No patient developed postembolization syndrome or progressive liver insufficiency after embolization or resection. One death after resection occurred as a result of sepsis and hemorrhage. Median hospital stays were 1 day after right PVE + IV and 7 days after resection.



Transhepatic ipsilateral right PVE + IV with use of particles and coils is a safe, effective method for inducing contralateral hypertrophy before extended right hepatectomy. Embolization with small spherical particles provides improved hypertrophy and resection rates compared with larger, nonspherical particles.

title: Extension of right portal vein embolization to segment IV portal branches.
abstract: Routine embolization of segment IV, combined with right portal vein embolization (PVE), has been suggested in patients who are candidates for right trisegmentectomy to induce higher and faster hypertrophy of segments II-III. Our objective was to compare hypertrophy of segments II-III induced by PVE with and without extension to segment IV in patients undergoing major hepatectomy.



Twenty-six consecutive patients were prospectively evaluated; the future remnant liver volume was calculated using the portal phase of spiral computed tomographic scans before and 3 to 4 weeks after right PVE (group R, n = 13), which was extended to segment IV branches in 13 patients (group L).



Twenty patients (76.9%) underwent the scheduled hepatic resection. Of the 6 patients who did not undergo the planned operation, 5 showed disease progression; in 1 patient (group L), there was an insufficient increase of the future remnant liver volume due to the presence of embolizing material in the left lobe. The mean +/- SD time between PVE and volume measurements was 31.8 +/- 9.3 days. The overall mean +/- SD future remnant liver volume increase was 53.1% +/- 24.8%; the increase for segment IV was significantly higher in group R than group L. The mean +/- SD post-PVE volumes of segments II-III and the rate of volume increase were similar in the 2 groups: group R, 348.4 +/- 83.1 cm3 and 67.8% +/- 30.8%, respectively, vs group L, 391.2 +/- 78.05 cm3 and 56.1% +/- 35.1%, respectively (P = .20 and P = .40).



Extension of embolization to segment IV portal branches should not be routinely used because a similar volume increase of segments II-III can be simply achieved by right PVE.

title: Mechanisms of Hepatic Regeneration Following Portal Vein Embolization and Partial Hepatectomy: A Review
abstract: BackgroundPortal vein embolization (PVE) improves outcome following major hepatectomy, and basic studies have presented evidence related to the mechanisms responsible for hepatic regeneration. Hemodynamic changes following PVE are similar to, but slightly different from, those of partial hepatectomy (PH) because arterial flow to the embolized lobe is preserved. However, the process of hepatic regeneration is essentially the same after both PVE and PH. A number of mediators are involved in PVE or PH-induced hepatic regeneration. These include inflammatory cytokines, vasoregulators, growth factors, eicosanoids, and various hormones. These mediators activate a complex network of signal transduction that promotes hepatic regeneration. A variety of conditions have been shown to modulate the function of these mediators and inhibit regeneration. These include biliary obstruction, diabetes, chronic ethanol consumption, malnutrition, gender, aging, and infection.ConclusionOptimizing these factors, where possible, before PVE or PH, is essential to maximize hypertrophy of the liver. A fuller understanding of hepatic physiology and pathophysiology following PVE or PH may lead to greater functional capacity of the remaining liver and extend the indications for hepatectomy in patients who require large liver volume resection.

title: Remnant liver volume to body weight ratio > or =0.5%: A new cut-off to estimate postoperative risks after extended resection in noncirrhotic liver.
abstract: Before extended hepatectomy of five or more segments, the remnant liver volume (RLV) is usually calculated as a ratio of RLV to total liver volume (RLV-TLV) and must be >20% to 25%. This method can lead to compare parts of normal liver parenchyma to others compromised by biliary or vascular obstruction or by portal vein embolization. Extrapolating from living-donor liver transplantation, we hypothesized that RLV to body weight ratio (RLV-BWR) could accurately assess the functional limit of hepatectomy.



From September 2000 to December 2004, volumetric measurements of RLV using computed tomography were obtained before right-extended hepatectomy in 31 patients. RLV-BWR of 0.5% as a critical point for patient course was compared with stratification by RLV-TLV (< or =25% or >25% and < or =20% or >20%).



Three-month morbidity and mortality were not significantly different between groups RLV-TLV < or = and >25% and between groups RLV-TLV < or = and >20%, but increased significantly in group RLV-BWR < or = 0.5% compared with group RLV-BWR > 0.5% (p = 0.038 and p = 0.019, respectively) with an non-significant increase in death from liver failure (p = 0.077).



RLV-BWR was more specific than RLV-TLV in predicting postoperative course after extended hepatectomy. Patients with an anticipated RLV < or = 0.5% of body weight are at considerable risk for hepatic dysfunction and postoperative mortality.

title: Comparison of Two Methods of Future Liver Remnant Volume Measurement
abstract: BackgroundIn liver transplantation, a minimum graft to patient body weight (BW) ratio is required for graft survival; in liver resection, total liver volume (TLV) calculated from body surface area (BSA) is used to determine the future liver remnant (FLR) volume needed for safe hepatic resection. These two methods of estimating liver volume have not previously been compared. The purpose of this study was to compare FLR volumes standardized to BW versus BSA and to assess their utility in predicting postoperative hepatic dysfunction after hepatic resection.MethodsRecords were reviewed of 68 consecutive noncirrhotic patients who underwent major hepatectomy after portal vein embolization between 1998 and 2006. FLR (cubic centimeter) was measured preoperatively with three-dimensional helical computed tomography; TLV (cubic centimeter) was calculated from the patients’ BSA. The relationship between FLR/TLV and FLR/BW (cubic centimeter per kilogram) was examined using linear regression analysis. Receiver operating characteristic (ROC) curve analysis was used to determine FLR/TLV and FLR/BW cutoff values for predicting postoperative hepatic dysfunction (defined as peak bilirubin level > 3 mg/dl or prothrombin time > 18 s).ResultsRegression analysis revealed that the FLR/TLV and FLR/BW ratios were highly correlated (Pearson correlation coefficient, 0.98). The area under the ROC curve was 0.85 for FLR/TLV and 0.84 for FLR/BW (95% confidence interval, 0.71–0.97). Sixteen of the 68 patients developed postoperative hepatic dysfunction. The ROC curve analysis yielded a cutoff FLR/BW value of ≤0.4, which had a positive predictive value (PPV) of 78% and a negative predictive value (NPV) of 85%. The corresponding FLR/TLV cutoff value of ≤20% had a PPV of 80% and a NPV of 86%.ConclusionsBased on the strong correlation between the FLR measurements standardized to BW and BSA and their similar ability to predict postoperative hepatic dysfunction, both methods are appropriate for assessing liver volume. In noncirrhotic patients, a FLR/BW ratio of ≤0.4 and FLR/TLV of ≤20% provide equivalent thresholds for performing safe hepatic resection.

title: Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection.
abstract: Recent reports highlighting reduced mortality rates to less than 1% after hepatic resections have evaluated the management of selected patients. The current risk of liver resection in unselected patients needs to be more clearly defined to appreciate the actual risk of new indications.



From 1990 to 1997, 747 consecutive patients, including 16 operated in emergency, underwent hepatic resection. Resection was indicated for malignancy in 473 patients (63%). Major resections were performed in 333 patients (45%). An underlying liver disease, including cirrhosis (n = 239) and obstructive jaundice (n = 4), was present in 253 patients (35%). Multivariate analysis of the risk factors for postoperative mortality, morbidity, and transfusion after stratifying patients for the circumstance of the operation and the pathological changes of the remnant liver was performed.



There was no intraoperative death and the overall mortality rate was 4.4%. This rate was 25% after emergency liver resection and 3.9% after elective liver resection (p < 0.001). After elective resection, mortality was significantly higher in patients with cirrhosis (8.7%) or obstructive jaundice (21%) than in patients with a normal liver (1%; p < 0.001). Analysis of this subgroup of 478 patients with normal liver showed that the mortality rate was 0% in 220 patients operated for a benign disease and in 263 patients who underwent minor resections. All five deaths occurred in patients with a malignancy and resulted from extrahepatic complications. In patients with a malignancy, the only independent predictor of death was an associated extrahepatic procedure. The incidence of postoperative complications was 22% and was influenced by the American Society of Anaesthesiology (ASA) score, extent of resection, presence of a steatosis, and an associated extrahepatic procedure. The incidence of major complications was 8% and of reoperation 3%. Perioperative blood transfusion was required in 112 of 478 (23%) and was not associated with increased mortality.



The 1% basic risk of elective liver resection on normal liver suggests that indications of resection for malignancy could be extended, unless an associated extrahepatic procedure is needed. Because of this low basic risk, future studies evaluating resection on normal liver should not consider in-hospital mortality as the only end point.

title: Portal vein embolization: rationale, technique and future prospects
abstract: Advances in surgery have reduced the mortality rate after major liver resection, but complications resulting from inadequate postresection hepatic size and function remain. Portal vein embolization (PVE) was proposed to induce hypertrophy of the anticipated liver remnant in order to reduce such complications. The techniques, measurement methods and indications for this treatment remain controversial.

title: Measurement of liver volume and hepatic functional reserve as a guide to decision-making in resectional surgery for hepatic tumors.
abstract: The respective volumes of hepatic tumors and nontumorous parenchyma of 50 patients requiring hepatectomy of more than one segment of Healey for tumor removal were measured using computed tomography (Vol-CT). The volume estimated by Vol-CT was found to correlate with the real weight resected (P < .0001) with a mean absolute error of 64.9 mL. The ratio of the nontumorous parenchymal volume of the resected liver to that of the whole liver (R2) in 15 patients who underwent right or extended right hepatic lobectomy was 43% +/- 15%. Eight of 15 patients with R2s < 60% underwent the procedures without right portal vein embolization (PE). The other seven with R2s exceeding 60% or an indocyanine green retention rate after 15 minutes (ICG15) of 10% to 20% underwent PE: in six of seven, the nontumorous parenchyma of the right hepatic lobe became atrophic and in all seven, the volume of the remaining left hepatic lobe increased with a decrease in the mean R2 from 62% +/- 14% to 55% +/- 8% (P = .0006). In the remaining 35 who underwent other hepatectomy procedures, R2s also remained <60%. Overall, at surgery, in 27 with normal liver function (ICG15 < 10%), R2s exceeded 60% in one, remained at 50% to 60% in five, and <50% in 21, whereas 23 patients except for one with an ICG15 exceeding 10%, had R2s of <50%. The postoperative serum total bilirubin levels in 84% of the patients remained within the normal range and there was no surgery-related mortality. In conclusion, 1) Vol-CT can accurately assess the extent of liver resection, 2) individuals with normal liver function can undergo resection of up to 60% of the nontumorous parenchyma without the need for PE, and 3) PE can be used to reduce the size of the resected tissue and increase the volume of the remnant liver to approximate the target limits in individuals with large tumors or minimally abnormal liver function.

title: Current role of portal vein embolization/hepatic artery chemoembolization.
abstract: This article has reviewed indications, methods, and results of PVE and TACE for hepatobiliary tumors. PVE is applied mainly to increase the safety of major hepatic resection in patients with hilar cholangiocarcinoma, HCC, or metastatic liver tumors. Hepatic arterial embolization causes selective ischemia of the liver tumor and enhances the cytotoxicity of the chemotherapeutic agent administered concomitantly. A survival benefit of TACE in patients with unresectable or recurrent HCC has been demonstrated. The significance of preoperative TACE is still controversial. TACE is routinely performed before PVE in HCC patients.

title: Preoperative Portal Vein Embolization for Extended Hepatectomy
abstract: ObjectiveTo examine the authors’ experience with preoperative ipsilateral portal vein embolization (PVE) and assess its role in extended hepatectomy.  DataExtended hepatectomy (five or more liver segments) has been associated with higher complication rates and increased postoperative liver dysfunction than have standard hepatic resections involving lesser volumes. Recently, PVE has been used in patients who have a predicted (postresection) future liver remnant (FLR) volume less than 25% of total liver volume in an attempt to increase the FLR and reduce complications. MethodsSixty patients from 1996 to 2002 were reviewed. Thirty-nine patients had PVE preoperatively. Eight patients who had PVE were not resected either due to the discovery of additional unresectable disease after embolization but before surgery (n = 5) or due to unresectable disease at surgery (n = 3). Therefore, 31 patients who had PVE subsequently underwent extended hepatic lobectomy. A comparable cohort of 21 patients who had an extended hepatectomy without PVE were selected on the basis of demographic, tumor, and liver volume characteristics. Patients had colorectal liver metastases (n = 30), hepatocellular carcinoma (n = 15), Klatskin tumors (n = 9), peripheral cholangiocarcinoma (n = 3), and other tumors (n = 3). The 52 resections performed included 42 extended right hepatectomies, 6 extended left hepatectomies, and 4 right hepatectomies extended to include the middle hepatic vein and the caudate lobe but preserving the majority of segment 4. Concomitant vascular reconstruction of either the inferior vena cava or hepatic veins was performed in five patients. ResultsThere were no differences between PVE and non-PVE groups in terms of tumor number, tumor size, tumor type, surgical margin status, complexity of operation, or perioperative red cell transfusion requirements. The predicted FLR was similar between PVE and non-PVE groups at presentation. After PVE the FLR was higher than in the non-PVE group. No complications were observed after PVE before resection. There was no difference in postoperative mortality, with one death from liver failure in the non-PVE group and no operative mortality in the PVE group. Postoperative peak bilirubin was higher in the non-PVE than the PVE group, as were postoperative fresh-frozen plasma requirements. Liver failure (defined as the development of encephalopathy, ascites requiring sustained diuretics or paracentesis, or coagulopathy unresponsive to vitamin K requiring fresh-frozen plasma after the first 24 hours postresection) was higher in the non-PVE patients than the PVE patients. The hospital stay was longer in the non-PVE than the PVE group.  PVE is a safe and effective method of increasing the remnant liver volume before extended hepatectomy. Increasing the remnant liver volume in patients with estimated postresection volumes of less than 25% appears to reduce postoperative liver dysfunction.

title: Changes in hepatic lobe volume in biliary tract cancer patients after right portal vein embolization
abstract: Changes in lobar volume of the liver and in total hepatic function were studied in 19 patients with biliary tract cancer who underwent right portal vein embolization as preoperative management for extensive liver resection. Computed tomography (CT) was performed to estimate liver volume before and approximately 11 days after embolization. An indocyanine green (ICG) test was performed before and 11 to 13 days after embolization. The calculated volume of the right lobe decreased from 761 ± 181 cm3 to 625 ± 110 cm3 11 days after embolization (P < .0001), whereas the volume of the left lobe increased from 420 ± 94 cm3 to 555 ± 110 cm3 (P < .0001). Thus, portal embolization produced a gain in left lobe volume of 136 ± 62 cm3 and an almost equivalent loss in right lobe volume. The hypertrophy ratio of the left lobe, expressed as percentage of postembolization volume of the left lobe to preembolization size, of the 5 patients with diabetes mellitus (DM) was lower than that of the 14 patients without diabetes (116.7 ± 6.3% vs. 140.4 ± 18.4%; P < .005). The ICG disappearance rate in 16 patients improved from 0.163 ± 0.163 ± 0.034 to 0.177 ± 0.027 (P < .05). The improvement was especially evident in 9 of 14 postjaundice patients, although the rate decreased slightly in 2 patients without jaundice. We conclude that right portal vein embolization can produce a compensatory hypertrophy of the left lobe within 11 days without seriously affecting hepatic function. In diabetic patients, however, a longer interval between embolization and operation may be needed to achieve sufficient hypertrophy of the left lobe. (HEPATOLOGY 1995;21:434–439.

title: Preoperative selective portal vein embolizations are an effective means of extending the indications of major hepatectomy in the normal and injured liver.
abstract: Liver tumors may be unresectable for volumetric reasons; the post-hepatectomy future remaining liver (FRL) will be too small to ensure survival. In some cases, preoperative selective portal vein embolization (PSPVE) of the tumorous part of the liver can permit the induction of hypertrophy of the FRL and convert patients from an unresectable to a resectable status.



Analysis of the efficiency of PSPVE in changing the volume of the FRL and in permitting curative hepatectomy was performed in a retrospective study of 28 initially unresectable (for volumetric reasons), consecutive cases treated from September 1987 to September 1995. Fifty percent of the cases had damaged liver parenchyma. PSPVE was performed in various locations, according to the site of the tumor and impairment of the liver parenchyma.



Twenty-five PSPVE (89%) successfully induced sufficient hypertrophy of the FRL. Explanations could be found retrospectively for the 3 failures. For the 28 cases, the mean increase in the FRL was 70%, and the mean ratio between the FRL and the whole functional liver changed from 21.5% before PSPVE, to 33.9% after PSPVE. Twenty-three patients could be hepatectomized (82%).



With this technique, liver tumors considered to be unresectable, due to life-threatening volumetric insufficiency, may be considered resectable lesions, and there is an increase in the safety of some extended hepatectomies. These good results were mainly due to application of the distal and proximal free flow embolization technique, with non-absorbable material, and perhaps to the long interval of one month between PSPVE and hepatectomy. Indications in normal liver parenchyma are for patients with a very small left lobe or those requiring a right hepatectomy with wedge resections of the left liver. Indications for damaged liver parenchyma also include some cases requiring left trisegmentectomy or central hepatectomy.

title: Percutaneous Portal Vein Embolization Increases the Feasibility and Safety of Major Liver Resection for Hepatocellular Carcinoma in Injured Liver
abstract: ObjectiveTo assess the influence of preoperative portal vein embolization (PVE) on the long-term outcome of liver resection for hepatocellular carcinoma (HCC) in injured liver.  an healthy liver, PVE of the liver to be resected induces hypertrophy of the remnant liver and increases the safety of hepatectomy. On injured liver, this effect is still debated. MethodsDuring the study period, 10 patients underwent preoperative PVE and 19 patients did not before resection of three or more liver segments for HCC in injured liver (cirrhosis or fibrosis). PVE was performed when the estimated rate of remnant functional liver parenchyma (ERRFLP) assessed by computed tomographic scan volumetry was less than 40%. ResultsIn all patients, PVE was feasible. There were no deaths or complications. The ERRFLP after PVE was significantly increased compared with the pre-PVE value. Liver resection was performed after PVE in 9 of 10 patients, with surgical death and complication rates of 0% and 45%, respectively. PVE increased the number of resections of three or more segments by 47% (9/19). Overall actuarial survival rates with or without previous PVE (89%, 67%, and 44% vs. 80%, 53%, and 53% at 1, 3 and 5 years, respectively) and disease-free actuarial survival rates (86%, 64%, and 21% vs. 55%, 17%, and 17% at 1, 3, and 5 years respectively) after hepatectomy were comparable. ConclusionWith the use of PVE, more patients with previously unresectable HCC in injured liver can benefit from resection. Long-term survival rates are comparable to those after resection without PVE.

title: Right Portal Vein Embolization Before Right Hepatectomy for Unilobar Colorectal Liver Metastases Reduces the Intrahepatic Recurrence Rate
abstract: To assess the effect of portal vein embolization (PVE) on intrahepatic recurrence rate after right hepatectomy for unilobar colorectal liver metastases (CLM). Recent research suggests that CLM could spread retrogradely through the portal vein. PVE may reduce tumor shedding by the occlusion of distal portal branches. However, no study reported the clinical effect of PVE on intrahepatic recurrence after CLM resection. Between 1995 and 2003, 44 patients requiring a right hepatectomy for unilobar CLM were operated in our institution. Right hepatectomy was performed after PVE in 23 patients (group A) and without PVE in 21 (group B). Surgical outcome and site of recurrence were analyzed. The postoperative mortality was nil. Overall morbidity and transitory liver failure rates were similar in groups A and B (43.4% and 17.3% vs. 33.3% and 14.2%, respectively). The 3- and 5-year overall survival rates did not differ in group A and B patients (61.2% and 43.7% vs. 49.7% and 35.5%, respectively; P = 0.862). The disease-free survival rate was similar in both groups. Thirty patients (68.2%) developed recurrences. Recurrences were intrahepatic in 22 patients (50%) and extrahepatic in 27 (61.3%). Intrahepatic recurrence rate was significantly lower in group A compared with group B (26.0% vs. 76.1% respectively; P < 0.001). PVE, number of CLM, and administration of neoadjuvant chemotherapy were independent prognostic factors for intrahepatic recurrences. This study showed that PVE reduces intrahepatic recurrence rate after right hepatectomy for unilobar CLM.

title: Preoperative portal vein embolization: indications and technical considerations.
abstract: Preoperative portal vein embolization (PVE) has become an important tool in the management of select patients before major hepatic resection. PVE redirects portal flow to the intended future remnant liver (FRL) to induce hypertrophy of the nondiseased portion of the liver and thereby may reduce complications and shorten hospital stays after surgery. This article reviews the technical considerations for performing PVE including the use of the ipsilateral or contralateral approaches, how to choose a particular embolic agent for PVE, the importance of liver volumetric measurements to estimate functional hepatic reserve, the pathophysiology of PVE, and some of the results showing the benefit of the procedure. In addition, the indications and contraindications for performing PVE in patients with and without chronic liver disease, the use of combination therapies, and the concern for tumor growth after PVE will be discussed.

title: Portal vein embolization before major hepatectomy and its effects on regeneration, resectability and outcome
abstract: This study evaluated the safety of portal vein embolization (PVE), its impact on future liver remnant (FLR) volume and regeneration, and subsequent effects on outcome after liver resection.

title: During liver regeneration following right portal embolization the growth rate of liver metastases is more rapid than that of the liver parenchyma
abstract: The relative growth rates of human liver metastases are not known. The aim of this study was to determine in humans the growth rate of liver parenchyma during regeneration and the growth rate of liver metastases during the same process.

title: Proliferative activity of intrahepatic colorectal metastases after preoperative hemihepatic portal vein embolization
abstract: Although hemihepatic portal vein embolization (PVE) has been used preoperatively to extend indications for hepatectomy in patients with colorectal metastases, the effects of this procedure on tumor growth and outcome remain controversial. To address this issue, we assessed the proliferative activity of intrahepatic metastases after PVE and the long‐term outcome of this procedure. Eighteen patients with colorectal metastases underwent preoperative PVE between 1996 and 2000 (PVE group). Twenty‐nine patients who underwent major hepatic resection without PVE served as control (non‐PVE group). The hepatic parenchymal fraction of the left lobe had significantly increased from 38.1 ± 3.2% to 45.9 ± 2.9% 3 weeks after PVE (+20.5%, P < .0001). Tumor volume and percent tumor volume had also significantly increased from 223 ± 89 mL to 270 ± 97 mL (+20.8%, P = .016) and from 13.7 + 4.3% to 16.2 + 4.9% (+18.5%, P = .014), respectively. There was no apparent correlation between the increase in parenchymal volume and that in tumor volume. The Ki‐67 labeling index of metastatic lesions was 46.6 ± 7.2% in the PVE group and 35.4 ± 12.6% in the non‐PVE group (P = .013). Long‐term survival was similar in the PVE and non‐PVE groups, however, disease‐free survival was significantly poorer in the PVE group than in the non‐PVE group (P = .004). We conclude that PVE increases tumor growth and probably is associated with enhanced recurrence of disease. Although PVE is effective in extending indications for surgery, patient selection for PVE should be cautious.

title: Research into the results of resection of hilar bile duct cancer.
abstract: We found mentions of 581 resections of hilar bile duct cancer in the literature to January 1989. Resection in 499 patients, reported or updated since 1980, resulted in an operative mortality of 12% and a 5-year survival rate of 13%. Resections confined to the hepatic duct confluence or extended to the quadrate lobe led to an 8% operative mortality and a 7% 5-year survival rate, although resections combined with major liver resection gave a 15% operative mortality and a 17% 5-year survival rate. Despite the best treatments available, present-day resection modalities are usually still not radical. Extension of resection in the retrohilar and hepatoduodenal direction might further improve the long-term surgical results.

title: Detection of hematogenic tumor cell dissemination in patients undergoing resection of liver metastases of colorectal cancer.
abstract: To determine the extent of pre- and intraoperative hematogenic tumor cell dissemination in patients undergoing liver resection for metastatic colorectal cancer.



For patients with hepatic metastases of colorectal cancer, liver resection is the only potentially curative therapy. However, 38% to 53% of patients develop extrahepatic tumor recurrence, probably caused by tumor cells disseminated before or during surgery not detected by current staging systems.



Blood samples harvested before, during, and after surgery from 41 patients and bone marrow samples from 30 patients undergoing resection of liver metastases of colorectal cancer were analyzed for disseminated tumor cells using cytokeratin 20 reverse transcriptase-polymerase chain reaction.



Tumor cells were detected in the blood samples of 26 of the 41 patients (63.4%) and in the bone marrow samples of 8 of the 30 patients (26.7%). Tumor cells were detected significantly more often during surgery than before or after surgery. Intraoperative tumor cell dissemination was detected in 41.7% of patients undergoing resection of two or more liver segments but only 14.3% of patients undergoing resection of one liver segment. Compared with resection of primary colorectal cancer, major liver resection carries an increased risk for intraoperative tumor cell dissemination.



Detection of disseminated tumor cells in patients undergoing liver resection for metastases of colorectal cancer using cytokeratin 20 reverse transcriptase-polymerase chain reaction might help to identify patients at high risk for tumor recurrence who may benefit from adjuvant therapy. Major liver resection of metastases leads to frequent intraoperative tumor cell shedding, possibly preventable by alternative surgical strategies.

title: Detection of hematogenous tumor cell dissemination predicts tumor relapse in patients undergoing surgical resection of colorectal liver metastases.
abstract: The mechanisms of hematogenous malignant spread have not been well understood. In certain cancers such as those of breast and colon, lymphatic spread is used as one parameter to direct postoperative adjuvant chemotherapy, assuming that the accompanying hematogenous spread will be mitigated and outcomes improved. These assumptions appear to be well founded in adjuvant chemotherapy trials reported for those 2 diseases. Identification of malignant cells in peripheral blood has been possible for many years using various methods, and advances in molecular biology techniques have improved detection; however, the fate of the cells and their clinical significance have been elusive. The current review by Weitz et al1 represents a continuation of one team's focus on malignant cells in both bone marrow and the peripheral circulation and the possible clinical impact of those cells on the patient. 
 
Fundamentally, the liver surgeon faced with a patient with metastatic disease has 2 decisions to make: that around the hepatectomy itself, and that involving subsequent adjuvant therapy. The surgeon is well aware of the outcome data derived from retrospective series indicating that certain factors will lead to an unfavorable result (tumor size, disease-free interval, nodal status of the primary tumor, number of liver tumors, and level of CEA),2 but these factors infrequently preclude surgery, especially as liver resection has become relatively safe in experienced hands and centers. Therefore, if any single measurement could improve the accuracy of prognosis in a specific patient, decision-making might be enhanced. 
 
The review by Weitz et al,1 like many retrospective studies, may provoke as many questions as it provides answers. For example, if we can identify any circulating malignant cells preoperatively, we may be tempted to consider neoadjuvant treatment, even though results in this study did not suggest that preoperative circulating cells predicted a worse prognosis and even though the fate of such cells remains unclear. If we can identify malignant cells postoperatively, perhaps the effects of adjuvant postoperative chemotherapy can be monitored by more than just a cursory clinical examination accompanied by CEA and imaging studies. The numbers of cases will always present challenges in hepatic resection-related evidence-based medicine as compared with the more common breast and colon cancers. In fact, recent studies reported by Cristofanilli et al3 have related clinical outcomes to circulating breast cancer cells. 
 
Perhaps the most sobering message in this paper is the suggestion of intraoperative “shedding” of cells, which may directly implicate the surgeon in upstaging the disease. The most common major liver resection for metastatic disease is a formal right hepatic lobectomy, whose accepted technique involves fairly vigorous manipulation and retraction of the liver prior to and even during removal; examination of malignant cells during either conventional or modified techniques (the so-called anterior approach to right hepatic lobectomy) might provide an answer to this technical question. 
 
Finally, Turnbull described in 19754 the “no-touch technique” for open colon resection, specifically to avoid tumor shedding from the primary cancer during operation. A reexamination of that technique, analogous to the anterior “no-manipulation” approach for liver surgery implied by this manuscript, may shed further light on the subject. 
 
Clearly, more work is needed to clarify what are interesting preliminary findings. Large-scale prospective studies are necessary to confirm the clinical significance of circulating epithelial tumor cells identified by assays such as RT-PCR of keratins. A prospective approach with controlled patient entry and interventions may ultimately offer to the surgical and medical oncologist various options that are better founded on stringent scientific principles; if improved surgery and more precise selection of patients for adjuvant therapy are forthcoming, those contributions will be significant.

title: Decreased Detection Rate of Disseminated Tumor Cells of Rectal Cancer Patients After Preoperative Chemoradiation: A First Step Towards a Molecular Surrogate Marker for Neoadjuvant Treatment in Colorectal Cancer
abstract: To compare the detection rates for rectal cancer cells in blood and bone marrow in patients with or without preoperative chemoradiation.  Previous reports have postulated a resistance of disseminated tumor cells to antiproliferative agents because of tumor cell dormancy.  Blood samples from 142 patients (pre, intra-, and postoperative samples) and bone marrow samples from 127 patients undergoing resection of rectal adenocarcinoma were analyzed for tumor cells using a cytokeratin (CK) 20-reverse transcription polymerase chain reaction. The results were stratified according to preoperative therapy.  In patients without preoperative chemoradiation, tumor cell detection in blood and bone marrow correlated to tumor stage (Cochran Armitage trend test, P < 0.05). Tumor cells were detected in 34 of 103 (33%) bone marrow and 65 of 117 (55.6%) blood samples of patients without neoadjuvant treatment versus in 4 of 24 (16.7%) bone marrow and in 10 of 25 (40%) blood samples of patients with neoadjuvant treatment. The tumor cell detection rate was significantly lower in the group having undergone chemoradiation (binary logistic regression analysis, P < 0.05). The overall and disease-free survival were significantly worse in patients with tumor cell detection in the bone marrow after neoadjuvant therapy.  Preoperative chemoradiation is associated with a decreased detection rate of rectal cancer cells in blood and bone marrow. These findings may explain the observed clinical benefit of patients with rectal cancer receiving chemoradiation. This is the first study suggesting that detection of disseminated rectal cancer cells may be useful for assessing the efficacy of neoadjuvant therapy.

title: Two-Stage Hepatectomy: A Planned Strategy to Treat Irresectable Liver Tumors
abstract: ObjectiveTo assess feasibility, risks, and patient outcomes in the treatment of colorectal metastases with two-stage hepatectomy.  DataSome patients with multiple hepatic colorectal metastases are not candidates for a complete resection by a single hepatectomy, even when downstaged by chemotherapy, after portal embolization, or combined with a locally destructive technique. In two-stage hepatectomy, the highest possible number of tumors is resected in a first, noncurative intervention, and the remaining tumors are resected after a period of liver regeneration. In selected patients with irresectable multiple metastases not amenable to a single hepatectomy procedure, two-stage hepatectomy might offer a chance of long-term remission. MethodsOf consecutive patients with conventionally irresectable colorectal metastases treated by chemotherapy, 16 of 398 (4%) became eligible for curative two-stage hepatectomy combined with chemotherapy and adjuvant nonsurgical interventions as indicated. ResultsTwo-stage hepatectomy was feasible in 13 of 16 patients (81%). There were no surgical deaths. The postoperative death rate (2 months or less) was 0% for the first-stage procedure and 15% for the second-stage one. Postoperative complication rates were 31% and 45%, respectively, with only one complication leading to reoperation. The 3-year survival rate was 35%, with four patients (31%) disease-free at 7, 22, 36, and 54 months. Median survival was 31 months from the second hepatectomy and 44 months from the diagnosis of metastases. ConclusionsTwo-stage hepatectomy combined with chemotherapy may allow a long-term remission in selected patients with irresectable multiple metastases and increases the proportion of patients with resectable disease.