Updates Surg (2014) 66:41–49 DOI 10.1007/s13304-013-0243-y
ORIGINAL ARTICLE
Defining indications to ALPPS procedure: technical aspects and open issues Francesca Ratti • Federica Cipriani • Annalisa Gagliano • Marco Catena • Michele Paganelli • Luca Aldrighetti
Received: 24 October 2013 / Accepted: 30 November 2013 / Published online: 17 December 2013 Ó Springer-Verlag Italia 2013
Abstract The limit to surgical treatment of patients with hepatic tumors is represented by the proportion of residual hepatic parenchyma at the end of surgery (FLR, future liver remnant) that provides an estimation of the risk of postoperative liver failure. Recently, a new two-stage technique has been developed with the acronym (ALPPS) associating liver partitioning and portal vein ligation for staged hepatectomy with the aim of obtaining a more rapid and effective increase in FLR, even though indications are not clear yet. Between January and December 2012, eight patients were candidates to ALPPS at the Hepatobiliary Surgery Unit of San Raffaele Hospital, Milan. The first three patients (Series 1) underwent right trisectionectomy and were affected by tumors infiltrating biliary confluence, while the others (Series 2) were candidates to right hepatectomy for colorectal liver metastases. Two patients were then excluded from Series 2 because intraoperative finding of irresectable disease. Intra- and postoperative outcome was evaluated with the aim of defining indications to ALPPS. All patients reached an adequate FLR after a median of 7.5 days from the first procedure (rate of program completion 100 %). In Series 1 two patients developed complications related to bile leakage from the raw surface of the liver to be resected and septic events secondary to ischemic necrosis of the liver segment IV. One patient died following multi-organ failure secondary to sepsis. In Series 2 postoperative course was uneventful in all the patients, and in particular no patient showed disease progression between the two procedures or signs of
F. Ratti (&) F. Cipriani A. Gagliano M. Catena M. Paganelli L. Aldrighetti General Surgery Department, Hepatobiliary Surgery Unit, IRCCS H San Raffaele, Via Olgettina 60, 20132 Milan, Italy e-mail: [email protected]
postoperative liver failure. ALPPS approach was initially considered suitable for patients affected by Klatskin tumors who require, despite a small tumor volume, extended hepatectomies associated with surgery of the biliary tract: the analysis of this first series of patients has led to a reevaluation of the indication to this strategy, as a consequence of encountered criticisms. Actually only a subset of patients affected by colorectal liver metastases are candidates to ALPPS. Keywords Liver resection Future liver remnant Hypetrophy Portal vein ligation In situ transection ALPPS
Introduction Liver surgery represents the only potentially curative treatment for many patients affected by primary and secondary hepatic malignancies. The pool of candidates to resection has progressively expanded in the past decades thanks to improvement in both surgical and anesthesiological management, leading to an acceptable rate of morbidity and mortality [1]. Actually, the only one factor limiting resectability is the volume of the future liver remnant (FLR), that affects the risk to develop postoperative liver failure (PLF) [2] development: in patients with normal parenchyma a FLR [25 % is enough to guarantee satisfactory postoperative function, while a FLR [40 % is mandatory in presence of underlying liver disease (cirrhosis, prolonged previous chemotherapy, cholestasis) [3, 4]. Techniques of portal vein occlusion (portal vein embolization, PVE; portal vein ligation, PVL) have been developed with the rationale of inducing FLR hypertrophy (10–50 % after a period of 2–8 weeks) thanks to a
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redistribution of portal flow within the liver [5–7]. The rate of completion of surgical program after these procedure ranges between 70 and 90 % depending on the series, with the most frequent reported causes of drop out represented by disease progression between portal occlusion and surgery and inadequate FLR hypertrophy [7, 8]. Recently, a novel two-stage approach has been proposed with the acronym ALPPS (associating liver partitioning and portal vein occlusion for staged hepatectomy) combining PVL and in situ parenchymal transection for right hepatectomy or trisectionectomy [9]: the aim should be to achieve a magnified hypertrophy in a shorter period of time, and therefore to allow an even further higher resectability rate. ALPPS series are still few and relevant significant morbidity and mortality rate are herein reported, but the main open issue still regards surgical indications that are not clear yet [10, 11]. Aim of this study was to analyze short-term outcome of a series collected in a short period of time in a single center, with the primary endpoint of defining indications to ALPPS to select the best pool of candidates to this approach, obtaining an expansion of surgical candidates while maintaining an acceptable morbidity rate that should be comparable with other strategies for hypertrophy of FLR.
Materials and methods Patients From January 2012 to December 2012, eight patients were candidates to ALPPS procedure at the Hepatobiliary Surgery Unit of San Raffaele Hospital, Milano. Data regarding these patients were prospectively collected and are now retrospectively reviewed. Three patients (Series 1) underwent ALPPS in the period between January and May for primary liver tumors with biliary confluence involvement (one patient was affected by gallbladder carcinoma, two patients were affected by Klatskin tumors Bismuth type IV) and requiring right hepatic trisectionectomy with biliary confluence resection. Five other patients (Series 2) in the following period were candidates to ALPPS for colorectal liver metastases (CLM) requiring right hepatectomy. Preoperative evaluation Before surgery, all patients were evaluated by thoracoabdominal imaging [computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP)] and blood tests including serum tumor markers levels [carcinoembryonic antigen (CEA) and Ca 19.9]. Selected patients also underwent positron emission tomography
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(PET), to evaluate the presence of extrahepatic disease. Preoperative chemotherapy was not routinely administrated in patients with cholangiocarcinoma, while a program of neoadjuvant treatment was planned in all the patients affected by colorectal liver metastases. Treatment strategies were systematically evaluated at weekly multidisciplinary meetings, including liver surgeons, radiologists and medical oncologists to define the final indication for the surgical procedure and both the type and the resection technique. Liver volumes assessment A CT was used to determine the volumes by threedimensional reconstruction of images. Total liver volume (TLV), tumor volume and resected volume were calculated before embolization using a dedicated software, multiplying the area of each liver session by the slice thickness. The FLR was estimated subtracting tumor volume as follows: (resected volume - tumor volume)/ (TLV - tumor volume). The FLR was re-assessed by CT scan at a median of 7.5 days after the first ALPPS stage, just before the hepatic resection. The liver hypertrophy was defined using the following ratio: (FLR after PVE - FLR pre PVE) 9 100/ (FLR pre PVE). The persistence of a FLR volume after PVE of less than 25 % (normal parenchyma) or less than 40 % (in other cases) was considered a contraindication to resection and a CT scan was carried out in an interval of 7 days, postponing the second surgical step. Indication for percutaneous transhepatic biliary drainage (PTBD) placement was obstructive jaundice or imaging evidence of bile ducts dilatation. Endoscopic drainage was avoided. External PTBD was preferred to external–internal drainage and bile replacement was not performed. Surgical procedures Stage I Abdominal incision consisted of a xipho-supraumbilical laparotomy prolonged to the right subcostal area. Abdominal exploration and intraoperative ultrasound through convex probe were used to determine resectability. The liver was mobilized through section of right triangular, coronary and falciform ligaments. Inferior vena cava was exposed after dissection of retrohepatic adhesions; minor hepatic veins were isolated and sectioned, until isolation of right hepatic vein on a vessel loop. Hepatoduodenal ligament was approached by the right side to isolate main hilar structures till their division into second-order branches. Right portal vein was isolated and sectioned. Bile duct management in Series 1 is described later (see ‘‘Results’’)
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while in Series 2 right bile duct was isolated and sectioned. Right hepatic artery was isolated and identified through a red-colored vessel loop. Portobiliary pedicles for segment IV were isolated on the right rim of the round ligament and sectioned to obtain parenchymal devascularization when right trisectionectomy was planned. Transection of the hepatic parenchyma was carried out by a combination of ultrasonic dissector and/or harmonic scalpel and wet bipolar forceps until the anterior aspect of the inferior vena cava was evident. Intermittent pringle maneuver was used on demand during liver transection, to control intraoperative blood loss. Middle hepatic vein, when its final ligation was planned, was isolated within the hepatic parenchyma and hanged on a vessel loop. Lymphadenectomy was routinely performed in Series 1 and consisted of removal of all lymph nodes and connective tissue in the hepatoduodenal ligament and retroduodenal area. Resection of liver segment I was always planned in patients affected by cholangiocarcinoma. In these patients, both distal and proximal margins of the sectioned bile ducts were sent for frozen section examination; the presence of neoplastic cells in examined sections constituted an indication for widening of margins, as far as technically feasible even performing multiple biliary enteric anastomoses. Roux-en-Y biliary enteric reconstruction was performed using a segment of jejunum: transanastomotic stenting was never performed. Before closing the abdominal wall, a surgical drain was placed within the transection plane and bioactive sealants were applied on the raw surface of the liver and its surroundings to prevent postoperative adhesions. Stage II The day following CT scan evaluation, all patients underwent second surgical step. The right artery was identified, ligated and sectioned. Whenever present, residual parenchymal bridges were transected till complete isolation of right hepatic vein and, when indicated, middle hepatic vein that were sectioned trough linear vascular stapler. In order to prevent liver rotation along its axis, the previously
sectioned falciform ligament was fixed anteriorly to the abdominal wall. At least one surgical drainage was placed near the transection plane. Outcome evaluation For each patient data regarding preoperative evaluation and staging were recorded, as well as data about liver volumes (FLR, TV, FLR increase). Intraoperative data and postoperative outcome were evaluated, including blood losses and transfusion rate, length of postoperative stay, morbidity and mortality. Postoperative complications were reviewed for 90 days following liver resection and were graded retrospectively according to Dindo–Clavien classification of surgical complications [11]. Postoperative mortality was defined as any death during postoperative hospitalization or within 90 days after resection. PLF was defined according to 50–50 criteria as defined by Balzan et al. [12] considering prothrombin time (PT) \50 % and serum bilirubin [50 lm/L on POD 5; PLF severity was staged according to the International Study Group of Liver Surgery (ISGLS) [13].
Results Preoperative baseline characteristics of patients belonging to Series 1 and 2 are reported in Table 1. Out of eight patients who were candidates to ALPPS approach, six completed the program: two patients, belonging to Series 2, were excluded and underwent laparotomy with evidence of peritoneal disseminated carcinomatosis in the first case and multiple unresectable bilobar liver metastases in the second. Series 1 All the patients belonging to Series 1 required right trisectionectomy with biliary confluence resection. All these patients presented at diagnosis with cholestatic
Table 1 Patients characteristics Patient
Age
Sex
ASA
Diagnosis
Cholestasis
Chronic liver disease
Previous CT
CT details
1
60
M
2
Hilar cholangioCA
Yes
No
No
NA
2
72
F
2
Gallbladder cancer
Yes
No
No
NA
3 4
65 52
M M
3 2
Hilar cholangioCA CLM
Yes No
No No
No Yes
NA Folfiri ? bevacizumab (12 cycles)
5
45
M
2
CLM
No
No
Yes
Folfox ? bevacizumab (6 cycles)
6
49
M
2
CLM
No
No
Yes
Folfiri ? cetuximab (8 cycles)
7
62
M
2
CLM
No
No
Yes
Folfiri (4 cycles)
8
64
F
2
CLM
No
No
Yes
Folfox ? cetuximab (8 cycles)
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Table 2 Drop out and volume analysis Patient
Drop out
Reason drop out
% FLR/TLV pre
% FLR/TLV post
FLR increase
Interval
1
No
NA
16
34
112.50
12
2
No
NA
24
31
29.,17
6
3
No
NA
19
32
68.42
8
4
No
NA
23
39
69.57
7
5
Yes
Unresectable liver disease
NA
NA
NA
NA
6
Yes
Peritoneal carcinomatosis
NA
NA
NA
NA
7
No
NA
21
31
47.62
8
8
No
NA
27
40
48.15
7
Median
7.5
Fig. 1 Patient with ischemic necrosis conditioning abscess of Segment 4 following 1st stage of ALPPS for hilar cholangiocarcinoma
jaundice and had an estimated FLR \40 % at preoperative evaluation (respectively 16, 21 and 26 %). In the first patient ALPPS procedure was not preoperatively planned (intraoperative finding of a more advanced disease compared to preoperative staging), while in the other two patients the program was defined before exploration. In the first case the biliary enteric anastomosis was performed during the second stage of ALPPS, while in the other two patients it was performed during the first intervention. All patients had a PTBD placed preoperatively through the right biliary tree to avoid significant biliary losses from the raw surface of the liver after parenchymal transection: indeed, biliary resection was planned during the first surgical step with subsequent biliary anastomosis on FLR and distal biliary suture on the liver to be removed. The first patient had been referred to our Institution with a PTBD already placed. In all the patients a satisfactory volume gain was recorded after a median of 7.5 days from the first surgical step, as shown in Table 2. R0 resection margins were achieved in all the patients.
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One patient had an uneventful postoperative course following the first surgical steps but developed gastrointestinal bleeding leading to severe anemia after the second stage. At endoscopic evaluation no active sources of bleeding were found even though a severe gastric hyperemia was recorded. The patient was treated by blood transfusions and high doses of proton pump inhibitors. He was discharged after 12 days from second stage. Other patients belonging to Series 1 required urgent relaparotomy after first stage: one developed an abscess within the ischemic segment IV, leading to sepsis and multi-organ failure (MOF) and requiring surgical resection of segment IV 2 days after first procedure (Fig. 1). Then, this patient needed intensive care management and died 9 days after second stage as a consequence of MOF. The other patient developed leukocytosis and fever, with associated severe abdominal distension and signs of sepsis: therefore, he underwent right extended hepatectomy 1 day before the planned surgical intervention. After the second stage he developed pleural effusion requiring drainage and mild signs of liver failure. Series 2 All patients belonging to Series 2 who begun ALPPS program (therefore excluding those undergoing staging laparotomy) completed the program thanks to significant FLR volume increase after a median of 7.5 days from the first intervention (Fig. 2a, b). Procedures combined with parenchymal transection and portal vein ligation during first step are reported in Table 3. A combined right colectomy and right hepatectomy was required in a patient with a FLR of 23 %, while the others had multiple bilobar lesions requiring a two stage program. No mortality was recorded and even morbidity related to liver surgery was nil. One patient (with combined rectal resection) developed pelvic abscess requiring drainage placement.
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Discussion
Fig. 2 a CT scan evaluation after 7 days from 1st stage of ALPPS in a patient with colorectal liver metastases. Hepatic veins axis. b CT scan evaluation after 7 days from 1st stage of ALPPS in a patient with colorectal liver metastases. Portal axis
The pool of candidates to liver resection for primary or secondary liver tumors has been expanded thanks to development of several techniques to increase the FLR and then the hepatic functional reserve, with the following rationale: by depriving of portal flow the parenchyma to be resected, the entire portal flow is redistributed towards the FLR constituting a stimulus to hypertrophy. The efficacy and safety of portal vein embolization (PVE) and intraoperative portal vein ligation (PVL) have been largely recognized in the literature; in 2008, a metaanalysis of 1,088 patients showed a mean percentage increase of FLR of 8–27 % after a mean interval of 29 days from PVE. A further stimulus to hypertrophy may be induced by portal infusion CD133 positive of stem cells, as reported in a study by Fu¨rst et al. [14]. Despite this, in a meta-analysis Abulkhir et al. [7] report a rate of drop-out from the surgical program of 15 % mainly as a consequence of progression of oncological disease and inadequate hypertrophy of the FLR. Moreover, in a recent review analyzing short- and long-term outcomes of largest series of two-stage hepatomies, a morbidity ranging between 20 and 60 % was reported after second surgical step and the rate of drop out ranged between 8 and 31 % [15]. Recently, a new approach to prevent the onset of hepatic failure in patients with small preoperative FLR has been proposed with the acronym ALPPS (associating liver partitioning and portal vein ligation for staged hepatectomy) [9, 16] and represents an evolution of the concept of two-stage hepatectomy first proposed by Adam et al. [17] and later modified by Jaeck et al. [18]. Patients are indeed candidates for a program of twostage hepatectomy: during the first step, PVL and in situ
Table 3 Surgical procedures, morbidity and mortality Patient
Procedure
1st step add. proced.
Complications 1st step
Grade
Complications 2nd step
Grade
PO Stay
1
Right trisectionectomy ? biliary confluence resection
Lymphadenectomy
Fever
II
GI bleeding
IIIa
22
2
Right trisectionectomy ? biliary confluence resection
Lymphadenectomy ? biliary enteric anastomosis
Renal failure, segment 4 ischemia
IV
Renal failure, MOF
V
3
3
Right trisectionectomy ? biliary confluence resection
Lymphadenectomy ? biliary enteric anastomosis
Segment 4 abscess, biliary leakage
IV
Pleural effusion
IIIa
30
4
Right hepatectomy
Right colectomy
None
–
None
–
9
5
Staging laparotomy
NA
NA
NA
NA
NA
NA
6
Staging laparotomy
NA
NA
NA
NA
NA
NA
7
Right hepatectomy
Left liver clearance ? rectal resection
None
–
Pelvic abscess
IIIa
20
8
Right hepatectomy
Left liver clearance
None
–
None
–
7
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Table 4 Literature review Study
Study design
No. of patients
Type of hepatectomy
N
Diagnosis
Schnitzbauer et al. [10]
Observative, descriptive
25 patients
Right trisectionectomy
25
Sala et al. [19]
Knoefel et al. [20]
Observative, descriptive
Comparative retrospective
5 centers
Li et al. [22]
Observative descriptive
3
Program conclusion 100 %
Intrahepatic cholangiocarcinoma
2
Klatskin
2
Hemangioendot.
1
Gallbladder cancer
1
CLM
15
Morbidity 64 %
NCLM
1
Mortality 12 % Program conclusion 100 %
4
HCC
1
Monoinstitutional
Right trisectionectomy
5
Klatskin
1
Left trisectionectomy
1
CLM
7
Morbidity: 40 %
NCLM
1
Mortality: 0 %
22 patients
HCC
1
Program conclusion 100 %
Monoinstitutional
Intrahepatic Cholangiocarcinoma
5
15 patients
Right hepatectomy
1
Klatskin
3
Right trisectionectomy
14
Gallbladder cancer
2
Right hepatectomy
0
CLM
10
Morbidity (ALPPS): 5/7pts
Right trisectionectomy
7
NCLM
1
Morbidity (PVE): 6/9pts Mortality: 0 %
HCC
1
Program conclusion 100 %
Klatskin
1
NA
Monoinstitutional
9 patients
Right hepatectomy
0
Monoinstitutional
Right trisectionectomy
9
transection of the parenchyma are performed. After a week, the volume of the FLR is re-assessed by imaging, so that the patient can undergo the second surgical step consisting of major hepatectomy. Primary goal of ALPPS is to obtain a faster increase in FLR compared to conventional portal vein occlusion obtained either surgically or radiologically, thus allowing an early hepatectomy avoiding the risk of tumor progression and exclusion from surgery. A review of studies published until now in the literature is represented in Table 4. In both, all series from the literature and present one, the rate of program completion was 100 %, meaning that no patient dropped out after the first operation. It should be underlined that further studies on larger series are needed to confirm that no chance of exclusion from second step of ALPPS may occur. So far, we still prefer to avoid prudentially to take any ‘‘one-way’’ solution during the first operation (e.g. placement of a plastic bag or tapes to be removed surgically) since the possibility of a drop out
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HCC
Right hepatectomy
7 ALPPS
Observative descriptive
Results
10 patients
15 PVE
Alvarez et al. [21]
N
CLM
10
Morbidity: 53 %
NCLM
3
Mortality: 0 %
Intrahepatic cholangiocarcinoma
3
Program conclusion 100 %
Klatskin
3
CLM
3
Mortality: 2 patients
cannot be excluded and the patient would then need a further surgical procedure even when not resectable. In this series, two drop-out patients were recorded at the moment of the first laparotomy, maybe reflecting that the pool of candidates to ALPPS is represented by borderline resectable patients and therefore the risk of unresectable disease (both hepatic and extrahepatic) is consistent. Schnitzbauer et al. described the first series of 25 cases completed in five centers in Germany; the study shows a FLR percentage increase of 74 % in 9 days, then faster and more effective compared to what normally occurs with vascular occlusion techniques alone [10]. Ideal candidates would thus be patients with a very small FLR (\20 %), who are not expected to achieve an adequate rate of hypertrophy with traditional techniques: the dramatic effect on liver regeneration is explained as a consequence of the interruption of collateral vessels between the two portions of parenchyma, which amplifies the effect of portal flux to FLR, hindering the
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recanalization of embolized portal branches. The parenchyma to be resected, in the interval between surgical steps, works as an auxiliary liver until its removal, once the FLR has reached an appropriate volume [9]. Knoefel et al. [20] compared the rate of parenchymal hypertrophy in a series of 22 patients undergoing isolated PVE (12 patients), ALPPS (7 patients) or the combination of the two procedures (3 patients) and reported a mean volume increase by 63 % after 3 days in patients undergoing ALPPS (volume gain of 22 % per day), significantly higher than the group treated with PVE alone. In addition, in patients who experience insufficient parenchymal growth after PVE, the ALPPS approach can still be evaluated as an option to convert them to resectability [20]. In the present study, as already reported in other literature series [10, 16, 19–21], the parenchymal transection carried out together with portal vein occlusion seems to give a benefit in terms of hypertrophy rate, especially if compared with a previous series of PVE from our institution which recorded a mean volumetric increase of 50.3 % [5]. Even the issue of tumoral progression in the interval between PVE and surgery, particularly evident in the nonembolized liver as demonstrated by Kokudo et al. [23], is partly obviated by ALPPS approach, as the interval before the curative resection is considerably reduced. Another reason to emphasize the value of this approach is the avoidance of FLR infiltration by the tumor, especially when located in the shelter of major vascular structures which should therefore be sacrificed in case of infiltration or encasement. The main drawback of this approach is the high rate of morbidity and mortality reported in the literature: Schnitzbauer [10] reported a morbidity of 64 % and a mortality rate of 12 %, while Knoefel [20] reported that only two out of 7 patients had a course free of complications. In the first period of the present series all patients developed postoperative complications, especially related to septic events secondary to ischemic necrosis of the liver segment IV, deprived of both vascular arterial and portal inflow. In order to prevent these complications, Andriani proposed the removal of the IV segment during the first surgical step [24]. Indeed, a patient in the present series developed segment IV necrosis and finally died for sepsis in spite of an intermediate surgical step for segment IV resection. Anyway, at the moment, series indicating the results of this additional procedure are still lacking in the literature. ALPPS technique should not be proposed with the aim of a complete replacement of traditional portal occlusion techniques, but with the main goal of expansion of the pool of candidates to surgery, rescuing those patients who are not supposed to be able to undergo surgical clearance of the liver after conventional techniques (PVE, PVL) either for inadequate FLR or tumor progression: in this setting,
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expected morbidity and mortality should be reappraised, taking into account that ALPPS corresponds to extreme hepatic surgery, associated with a rate of complication significantly higher compared to conventional major hepatic surgery. In the first period of this study indeed, indications to ALPPS procedure were considered: (1) severely inadequate FLR (\20 %) (2) need for surgical exploration for resectability assessment (as in locally advanced tumors or neoplasms infiltrating the hilum) (3) intraoperative findings consistent with more advanced disease compared to preoperative staging (4) high risk of rapid progression of disease. In our institution, as reported in first series [22], ALPPS approach was therefore initially considered suitable for the treatment of patients affected by Klatskin tumors who require, despite a small tumor volume, extended hepatectomies associated with surgery of the biliary tract: the analysis of this first series of patients has led to a reevaluation of the indication to this strategy, as a consequence of encountered criticisms. Relevant morbidity reported in Series 1 of this study was mainly related to complications secondary to ischemic necrosis and abscess of segment IV, deprived of both arterial and venous vascularization, in patient who had experienced prolonged cholestasis due to biliary tree infiltration by the tumor. Indeed both these conditions (segment IV devascularization and cholestasis) represent risk factors for postoperative adverse events. Li et al. in a recent series of ALPPS found that patients requiring biliary drainage for biliary strictures had an higher risk of infections and bile leak compared to others, concluding that patients with Klatskin tumors have additional risk factors for intraabdominal infection and bacteraemia so that cholestatic liver with lower regeneration potential have been considered by these authors a contraindication to ALPPS [22]. These facts, along with the considerations of Aloia who defines ALPPS ‘‘all touch technique’’ [25], opposed to the ‘‘no-touch’’ described by Neuhaus et al. [26], (due to intraoperative manipulation of portobiliary hilar structures and need of leaving in place the neoplasm after the first surgical step), led to a shift in ALPPS indication, as regards both the type of intervention and the treated pathology. In Series 2 indeed, candidates to ALPPS were patients requiring right hepatectomy for CLM (no need for segment IV resection in patients without prolonged cholestasis). ALPPS procedure, performed in this setting, seems to be safe and feasible in a selected population of patients, allowing obtaining of an acceptable rate of morbidity and mortality. In the current practice of our Institution, ALPPS indications are the following for CLM: (1) two-stage
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hepatectomy, (2) liver metastases surgery combined with colorectal cancer resection (FLR \20 % when healthy liver; FLR \30 % if CALI-chemotherapy associated liver injury), (3) intraoperative finding of bilobar lesions, without possibility of clearance in a single step. In the present series, the issue regarding the difference between volume increase and functional reserve gain has not been specifically addressed: despite this, it should be postulated that signs of PLF in patients undergoing ALPPS and experiencing adequate volume increase are related to a still insufficient and/or impaired parenchymal functional reserve. This phenomenon is similar to what reported in patients undergoing liver transplantation and developing small for size syndrome, when portal hyperafflux causes both a functional and structural damage to liver parenchyma [27, 28]. In conclusion, ALPPS approach allows to expand the number of candidates to surgical treatment thanks to the possibility of achieving an higher rate of hypertrophy in a shorter time compared to traditional techniques of vascular occlusion. The high rate of morbidity and mortality related to biliary and septic complications leads to a shift in indications toward patients with liver metastases from colorectal cancer who require right hepatectomy. Conflict of interest
None.
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22.
23.
embolization before liver resection: a systematic review. Cardiovasc Intervent Radiol 36(1):25–34 De Santibanes E, Clavien PA (2012) Playing Play-Doh to prevent postoperative liver failure: the ‘‘ALPPS’’ approach. Ann Surg 255(3):415–417 Schnitzbauer AA, Lang SA, Goessmann H, Nadalin S, Baumgart J, Farkas SA, Fichtner-Feigl S, Lorf T, Goralcyk A, Horbelt R, Kroemer A, Loss M, Rummele P, Scherer MN, Padberg W, Konigsrainer A, Lang H, Obed A, Schlitt HJ (2012) Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small for size settings. Ann Surg 255(3):405–414 Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240(2):205–213 Balzan S, Belghiti J, Farges O, Ogata S, Sauvanet A, Delefosse D, Durand F (2005) The ‘‘50-50 criteria’’ on postoperative day 5:an accurate predictor of liver failure and death after hepatectomy. Ann Surg 242(6):824–828 Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, Koch M, Makuuchi M, Dematteo RP, Christophi C, Banting S, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Yokoyama Y, Fan ST, Nimura Y, Figueras J, Capussotti L, Buchler MW, Weitz J (2011) Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery 149(5):713–724 Fu¨rst G, Schulte am Esch J, Poll LW, Hosch SB, Fritz LB, Klein M, Godehardt E, Krieg A, Wecker B, Stoldt V, Stockschla¨der M, Eisenberger CF, Mo¨dder U, Knoefel WT (2007) Portal vein embolization and autologous CD133 ? bone marrow stem cells for liver regeneration: initial experience. Radiology 243:171–179 Lam VW, Laurence JM, Johnston E, Hollands MJ, Pleass HC, Richardson AJ (2013) A systematic review of two-stage hepatectomy in patients with initially unresectable colorectal liver metastases. HPB 15(7):483–491 De Santibanes E, Alvarez FA, Ardiles V (2012) How to avoid postoperative liver failure: a novel method. World J Surg 36:125–128 Adam R, Laurent A, Azoulay D, Castaing D, Bismuth H (2000) Two stage hepatectomy: a planned strategy to treat irresectable liver tumors. Ann Surg 232(6):777–785 Jaeck D, Oussoultzoglou E, Rosso E, Greget M, Weber JC, Bachellier P (2004) A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple an bilobar liver metastases. Ann Surg 240(6):1037–1049 Sala S, Ardiles V, Ulla M, Alvarez F, Pekoli J, de Santibanes E (2012) Our initial experience with ALPPS technique: encouraging results. Updates Surg 64(3):167–172 Knoefel WT, Gabor I, Rehders A, Alexander A, Krausch M, Schukte am Esch J, Fu¨rst G, Topp SA (2013) In situ liver transection with portal vein ligation for rapid growth of the future liver remnant in two-stage liver resection. Br J Surg 100(3):388–394 Alvarez FA, Ardiles V, Sanchez Claria R, Pekoli J, de Santibanes E (2012) Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS):tips and tricks. J Gastrointest Surg 17(4):814–821 Li J, Girotti P, Konigsrainer I, Ladurner R, Konigsrainer A, Nadalin S (2013) ALPPS in right trisectionectomy: a safe procedure to avoid postoperative liver failure? J Gastrointest Surg 17(5):956–961 Kokudo N, Tada K, Seki M, Ohta H, Azekura K, Ueno M, Ohta K, Yamaguchi T, Matsubara T, Takahashi T, Nakajima T, Muto
Updates Surg (2014) 66:41–49 T, Ikari T, Yanagisawa A, Kato Y (2001) Proliferative activity of intrahepatic colorectal metastases after preoperative hemihepatic portal vein embolization. Hepatology 34(2):267–272 24. Andriani OC (2012) Long-term results with associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). Ann Surg 256(3):e5 25. Aloia TA, Vauthey JN (2012) Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): what is gained and what is lost? Ann Surg 256(3):e9 26. Neuhaus P, Thelen A, Jonas S, Puhl G, Denecke T, VeltzkeSchlieker W, Seehofer D (2012) Oncological superiority of hilar
49 en bloc resection for the treatment of hilar cholangiocarcinoma. Ann Surg Oncol 19(5):1602–1608 27. Yagi S, Uemoto S (2012) Small-for-size syndrome in living donor liver transplantation. Hepatobiliary Pancreat Dis Int 11(6):570–576 28. Hammond JS, guha IN, Beckingham IJ, Lobo DN (2011) Prediction, prevention and management of postresection liver failure. Br J Surg 98(9):1188–1200
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ORIGINAL ARTICLE
Defining indications to ALPPS procedure: technical aspects and open issues Francesca Ratti • Federica Cipriani • Annalisa Gagliano • Marco Catena • Michele Paganelli • Luca Aldrighetti
Received: 24 October 2013 / Accepted: 30 November 2013 / Published online: 17 December 2013 Ó Springer-Verlag Italia 2013
Abstract The limit to surgical treatment of patients with hepatic tumors is represented by the proportion of residual hepatic parenchyma at the end of surgery (FLR, future liver remnant) that provides an estimation of the risk of postoperative liver failure. Recently, a new two-stage technique has been developed with the acronym (ALPPS) associating liver partitioning and portal vein ligation for staged hepatectomy with the aim of obtaining a more rapid and effective increase in FLR, even though indications are not clear yet. Between January and December 2012, eight patients were candidates to ALPPS at the Hepatobiliary Surgery Unit of San Raffaele Hospital, Milan. The first three patients (Series 1) underwent right trisectionectomy and were affected by tumors infiltrating biliary confluence, while the others (Series 2) were candidates to right hepatectomy for colorectal liver metastases. Two patients were then excluded from Series 2 because intraoperative finding of irresectable disease. Intra- and postoperative outcome was evaluated with the aim of defining indications to ALPPS. All patients reached an adequate FLR after a median of 7.5 days from the first procedure (rate of program completion 100 %). In Series 1 two patients developed complications related to bile leakage from the raw surface of the liver to be resected and septic events secondary to ischemic necrosis of the liver segment IV. One patient died following multi-organ failure secondary to sepsis. In Series 2 postoperative course was uneventful in all the patients, and in particular no patient showed disease progression between the two procedures or signs of
F. Ratti (&) F. Cipriani A. Gagliano M. Catena M. Paganelli L. Aldrighetti General Surgery Department, Hepatobiliary Surgery Unit, IRCCS H San Raffaele, Via Olgettina 60, 20132 Milan, Italy e-mail: [email protected]
postoperative liver failure. ALPPS approach was initially considered suitable for patients affected by Klatskin tumors who require, despite a small tumor volume, extended hepatectomies associated with surgery of the biliary tract: the analysis of this first series of patients has led to a reevaluation of the indication to this strategy, as a consequence of encountered criticisms. Actually only a subset of patients affected by colorectal liver metastases are candidates to ALPPS. Keywords Liver resection Future liver remnant Hypetrophy Portal vein ligation In situ transection ALPPS
Introduction Liver surgery represents the only potentially curative treatment for many patients affected by primary and secondary hepatic malignancies. The pool of candidates to resection has progressively expanded in the past decades thanks to improvement in both surgical and anesthesiological management, leading to an acceptable rate of morbidity and mortality [1]. Actually, the only one factor limiting resectability is the volume of the future liver remnant (FLR), that affects the risk to develop postoperative liver failure (PLF) [2] development: in patients with normal parenchyma a FLR [25 % is enough to guarantee satisfactory postoperative function, while a FLR [40 % is mandatory in presence of underlying liver disease (cirrhosis, prolonged previous chemotherapy, cholestasis) [3, 4]. Techniques of portal vein occlusion (portal vein embolization, PVE; portal vein ligation, PVL) have been developed with the rationale of inducing FLR hypertrophy (10–50 % after a period of 2–8 weeks) thanks to a
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redistribution of portal flow within the liver [5–7]. The rate of completion of surgical program after these procedure ranges between 70 and 90 % depending on the series, with the most frequent reported causes of drop out represented by disease progression between portal occlusion and surgery and inadequate FLR hypertrophy [7, 8]. Recently, a novel two-stage approach has been proposed with the acronym ALPPS (associating liver partitioning and portal vein occlusion for staged hepatectomy) combining PVL and in situ parenchymal transection for right hepatectomy or trisectionectomy [9]: the aim should be to achieve a magnified hypertrophy in a shorter period of time, and therefore to allow an even further higher resectability rate. ALPPS series are still few and relevant significant morbidity and mortality rate are herein reported, but the main open issue still regards surgical indications that are not clear yet [10, 11]. Aim of this study was to analyze short-term outcome of a series collected in a short period of time in a single center, with the primary endpoint of defining indications to ALPPS to select the best pool of candidates to this approach, obtaining an expansion of surgical candidates while maintaining an acceptable morbidity rate that should be comparable with other strategies for hypertrophy of FLR.
Materials and methods Patients From January 2012 to December 2012, eight patients were candidates to ALPPS procedure at the Hepatobiliary Surgery Unit of San Raffaele Hospital, Milano. Data regarding these patients were prospectively collected and are now retrospectively reviewed. Three patients (Series 1) underwent ALPPS in the period between January and May for primary liver tumors with biliary confluence involvement (one patient was affected by gallbladder carcinoma, two patients were affected by Klatskin tumors Bismuth type IV) and requiring right hepatic trisectionectomy with biliary confluence resection. Five other patients (Series 2) in the following period were candidates to ALPPS for colorectal liver metastases (CLM) requiring right hepatectomy. Preoperative evaluation Before surgery, all patients were evaluated by thoracoabdominal imaging [computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP)] and blood tests including serum tumor markers levels [carcinoembryonic antigen (CEA) and Ca 19.9]. Selected patients also underwent positron emission tomography
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Updates Surg (2014) 66:41–49
(PET), to evaluate the presence of extrahepatic disease. Preoperative chemotherapy was not routinely administrated in patients with cholangiocarcinoma, while a program of neoadjuvant treatment was planned in all the patients affected by colorectal liver metastases. Treatment strategies were systematically evaluated at weekly multidisciplinary meetings, including liver surgeons, radiologists and medical oncologists to define the final indication for the surgical procedure and both the type and the resection technique. Liver volumes assessment A CT was used to determine the volumes by threedimensional reconstruction of images. Total liver volume (TLV), tumor volume and resected volume were calculated before embolization using a dedicated software, multiplying the area of each liver session by the slice thickness. The FLR was estimated subtracting tumor volume as follows: (resected volume - tumor volume)/ (TLV - tumor volume). The FLR was re-assessed by CT scan at a median of 7.5 days after the first ALPPS stage, just before the hepatic resection. The liver hypertrophy was defined using the following ratio: (FLR after PVE - FLR pre PVE) 9 100/ (FLR pre PVE). The persistence of a FLR volume after PVE of less than 25 % (normal parenchyma) or less than 40 % (in other cases) was considered a contraindication to resection and a CT scan was carried out in an interval of 7 days, postponing the second surgical step. Indication for percutaneous transhepatic biliary drainage (PTBD) placement was obstructive jaundice or imaging evidence of bile ducts dilatation. Endoscopic drainage was avoided. External PTBD was preferred to external–internal drainage and bile replacement was not performed. Surgical procedures Stage I Abdominal incision consisted of a xipho-supraumbilical laparotomy prolonged to the right subcostal area. Abdominal exploration and intraoperative ultrasound through convex probe were used to determine resectability. The liver was mobilized through section of right triangular, coronary and falciform ligaments. Inferior vena cava was exposed after dissection of retrohepatic adhesions; minor hepatic veins were isolated and sectioned, until isolation of right hepatic vein on a vessel loop. Hepatoduodenal ligament was approached by the right side to isolate main hilar structures till their division into second-order branches. Right portal vein was isolated and sectioned. Bile duct management in Series 1 is described later (see ‘‘Results’’)
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43
while in Series 2 right bile duct was isolated and sectioned. Right hepatic artery was isolated and identified through a red-colored vessel loop. Portobiliary pedicles for segment IV were isolated on the right rim of the round ligament and sectioned to obtain parenchymal devascularization when right trisectionectomy was planned. Transection of the hepatic parenchyma was carried out by a combination of ultrasonic dissector and/or harmonic scalpel and wet bipolar forceps until the anterior aspect of the inferior vena cava was evident. Intermittent pringle maneuver was used on demand during liver transection, to control intraoperative blood loss. Middle hepatic vein, when its final ligation was planned, was isolated within the hepatic parenchyma and hanged on a vessel loop. Lymphadenectomy was routinely performed in Series 1 and consisted of removal of all lymph nodes and connective tissue in the hepatoduodenal ligament and retroduodenal area. Resection of liver segment I was always planned in patients affected by cholangiocarcinoma. In these patients, both distal and proximal margins of the sectioned bile ducts were sent for frozen section examination; the presence of neoplastic cells in examined sections constituted an indication for widening of margins, as far as technically feasible even performing multiple biliary enteric anastomoses. Roux-en-Y biliary enteric reconstruction was performed using a segment of jejunum: transanastomotic stenting was never performed. Before closing the abdominal wall, a surgical drain was placed within the transection plane and bioactive sealants were applied on the raw surface of the liver and its surroundings to prevent postoperative adhesions. Stage II The day following CT scan evaluation, all patients underwent second surgical step. The right artery was identified, ligated and sectioned. Whenever present, residual parenchymal bridges were transected till complete isolation of right hepatic vein and, when indicated, middle hepatic vein that were sectioned trough linear vascular stapler. In order to prevent liver rotation along its axis, the previously
sectioned falciform ligament was fixed anteriorly to the abdominal wall. At least one surgical drainage was placed near the transection plane. Outcome evaluation For each patient data regarding preoperative evaluation and staging were recorded, as well as data about liver volumes (FLR, TV, FLR increase). Intraoperative data and postoperative outcome were evaluated, including blood losses and transfusion rate, length of postoperative stay, morbidity and mortality. Postoperative complications were reviewed for 90 days following liver resection and were graded retrospectively according to Dindo–Clavien classification of surgical complications [11]. Postoperative mortality was defined as any death during postoperative hospitalization or within 90 days after resection. PLF was defined according to 50–50 criteria as defined by Balzan et al. [12] considering prothrombin time (PT) \50 % and serum bilirubin [50 lm/L on POD 5; PLF severity was staged according to the International Study Group of Liver Surgery (ISGLS) [13].
Results Preoperative baseline characteristics of patients belonging to Series 1 and 2 are reported in Table 1. Out of eight patients who were candidates to ALPPS approach, six completed the program: two patients, belonging to Series 2, were excluded and underwent laparotomy with evidence of peritoneal disseminated carcinomatosis in the first case and multiple unresectable bilobar liver metastases in the second. Series 1 All the patients belonging to Series 1 required right trisectionectomy with biliary confluence resection. All these patients presented at diagnosis with cholestatic
Table 1 Patients characteristics Patient
Age
Sex
ASA
Diagnosis
Cholestasis
Chronic liver disease
Previous CT
CT details
1
60
M
2
Hilar cholangioCA
Yes
No
No
NA
2
72
F
2
Gallbladder cancer
Yes
No
No
NA
3 4
65 52
M M
3 2
Hilar cholangioCA CLM
Yes No
No No
No Yes
NA Folfiri ? bevacizumab (12 cycles)
5
45
M
2
CLM
No
No
Yes
Folfox ? bevacizumab (6 cycles)
6
49
M
2
CLM
No
No
Yes
Folfiri ? cetuximab (8 cycles)
7
62
M
2
CLM
No
No
Yes
Folfiri (4 cycles)
8
64
F
2
CLM
No
No
Yes
Folfox ? cetuximab (8 cycles)
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Table 2 Drop out and volume analysis Patient
Drop out
Reason drop out
% FLR/TLV pre
% FLR/TLV post
FLR increase
Interval
1
No
NA
16
34
112.50
12
2
No
NA
24
31
29.,17
6
3
No
NA
19
32
68.42
8
4
No
NA
23
39
69.57
7
5
Yes
Unresectable liver disease
NA
NA
NA
NA
6
Yes
Peritoneal carcinomatosis
NA
NA
NA
NA
7
No
NA
21
31
47.62
8
8
No
NA
27
40
48.15
7
Median
7.5
Fig. 1 Patient with ischemic necrosis conditioning abscess of Segment 4 following 1st stage of ALPPS for hilar cholangiocarcinoma
jaundice and had an estimated FLR \40 % at preoperative evaluation (respectively 16, 21 and 26 %). In the first patient ALPPS procedure was not preoperatively planned (intraoperative finding of a more advanced disease compared to preoperative staging), while in the other two patients the program was defined before exploration. In the first case the biliary enteric anastomosis was performed during the second stage of ALPPS, while in the other two patients it was performed during the first intervention. All patients had a PTBD placed preoperatively through the right biliary tree to avoid significant biliary losses from the raw surface of the liver after parenchymal transection: indeed, biliary resection was planned during the first surgical step with subsequent biliary anastomosis on FLR and distal biliary suture on the liver to be removed. The first patient had been referred to our Institution with a PTBD already placed. In all the patients a satisfactory volume gain was recorded after a median of 7.5 days from the first surgical step, as shown in Table 2. R0 resection margins were achieved in all the patients.
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One patient had an uneventful postoperative course following the first surgical steps but developed gastrointestinal bleeding leading to severe anemia after the second stage. At endoscopic evaluation no active sources of bleeding were found even though a severe gastric hyperemia was recorded. The patient was treated by blood transfusions and high doses of proton pump inhibitors. He was discharged after 12 days from second stage. Other patients belonging to Series 1 required urgent relaparotomy after first stage: one developed an abscess within the ischemic segment IV, leading to sepsis and multi-organ failure (MOF) and requiring surgical resection of segment IV 2 days after first procedure (Fig. 1). Then, this patient needed intensive care management and died 9 days after second stage as a consequence of MOF. The other patient developed leukocytosis and fever, with associated severe abdominal distension and signs of sepsis: therefore, he underwent right extended hepatectomy 1 day before the planned surgical intervention. After the second stage he developed pleural effusion requiring drainage and mild signs of liver failure. Series 2 All patients belonging to Series 2 who begun ALPPS program (therefore excluding those undergoing staging laparotomy) completed the program thanks to significant FLR volume increase after a median of 7.5 days from the first intervention (Fig. 2a, b). Procedures combined with parenchymal transection and portal vein ligation during first step are reported in Table 3. A combined right colectomy and right hepatectomy was required in a patient with a FLR of 23 %, while the others had multiple bilobar lesions requiring a two stage program. No mortality was recorded and even morbidity related to liver surgery was nil. One patient (with combined rectal resection) developed pelvic abscess requiring drainage placement.
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Discussion
Fig. 2 a CT scan evaluation after 7 days from 1st stage of ALPPS in a patient with colorectal liver metastases. Hepatic veins axis. b CT scan evaluation after 7 days from 1st stage of ALPPS in a patient with colorectal liver metastases. Portal axis
The pool of candidates to liver resection for primary or secondary liver tumors has been expanded thanks to development of several techniques to increase the FLR and then the hepatic functional reserve, with the following rationale: by depriving of portal flow the parenchyma to be resected, the entire portal flow is redistributed towards the FLR constituting a stimulus to hypertrophy. The efficacy and safety of portal vein embolization (PVE) and intraoperative portal vein ligation (PVL) have been largely recognized in the literature; in 2008, a metaanalysis of 1,088 patients showed a mean percentage increase of FLR of 8–27 % after a mean interval of 29 days from PVE. A further stimulus to hypertrophy may be induced by portal infusion CD133 positive of stem cells, as reported in a study by Fu¨rst et al. [14]. Despite this, in a meta-analysis Abulkhir et al. [7] report a rate of drop-out from the surgical program of 15 % mainly as a consequence of progression of oncological disease and inadequate hypertrophy of the FLR. Moreover, in a recent review analyzing short- and long-term outcomes of largest series of two-stage hepatomies, a morbidity ranging between 20 and 60 % was reported after second surgical step and the rate of drop out ranged between 8 and 31 % [15]. Recently, a new approach to prevent the onset of hepatic failure in patients with small preoperative FLR has been proposed with the acronym ALPPS (associating liver partitioning and portal vein ligation for staged hepatectomy) [9, 16] and represents an evolution of the concept of two-stage hepatectomy first proposed by Adam et al. [17] and later modified by Jaeck et al. [18]. Patients are indeed candidates for a program of twostage hepatectomy: during the first step, PVL and in situ
Table 3 Surgical procedures, morbidity and mortality Patient
Procedure
1st step add. proced.
Complications 1st step
Grade
Complications 2nd step
Grade
PO Stay
1
Right trisectionectomy ? biliary confluence resection
Lymphadenectomy
Fever
II
GI bleeding
IIIa
22
2
Right trisectionectomy ? biliary confluence resection
Lymphadenectomy ? biliary enteric anastomosis
Renal failure, segment 4 ischemia
IV
Renal failure, MOF
V
3
3
Right trisectionectomy ? biliary confluence resection
Lymphadenectomy ? biliary enteric anastomosis
Segment 4 abscess, biliary leakage
IV
Pleural effusion
IIIa
30
4
Right hepatectomy
Right colectomy
None
–
None
–
9
5
Staging laparotomy
NA
NA
NA
NA
NA
NA
6
Staging laparotomy
NA
NA
NA
NA
NA
NA
7
Right hepatectomy
Left liver clearance ? rectal resection
None
–
Pelvic abscess
IIIa
20
8
Right hepatectomy
Left liver clearance
None
–
None
–
7
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Table 4 Literature review Study
Study design
No. of patients
Type of hepatectomy
N
Diagnosis
Schnitzbauer et al. [10]
Observative, descriptive
25 patients
Right trisectionectomy
25
Sala et al. [19]
Knoefel et al. [20]
Observative, descriptive
Comparative retrospective
5 centers
Li et al. [22]
Observative descriptive
3
Program conclusion 100 %
Intrahepatic cholangiocarcinoma
2
Klatskin
2
Hemangioendot.
1
Gallbladder cancer
1
CLM
15
Morbidity 64 %
NCLM
1
Mortality 12 % Program conclusion 100 %
4
HCC
1
Monoinstitutional
Right trisectionectomy
5
Klatskin
1
Left trisectionectomy
1
CLM
7
Morbidity: 40 %
NCLM
1
Mortality: 0 %
22 patients
HCC
1
Program conclusion 100 %
Monoinstitutional
Intrahepatic Cholangiocarcinoma
5
15 patients
Right hepatectomy
1
Klatskin
3
Right trisectionectomy
14
Gallbladder cancer
2
Right hepatectomy
0
CLM
10
Morbidity (ALPPS): 5/7pts
Right trisectionectomy
7
NCLM
1
Morbidity (PVE): 6/9pts Mortality: 0 %
HCC
1
Program conclusion 100 %
Klatskin
1
NA
Monoinstitutional
9 patients
Right hepatectomy
0
Monoinstitutional
Right trisectionectomy
9
transection of the parenchyma are performed. After a week, the volume of the FLR is re-assessed by imaging, so that the patient can undergo the second surgical step consisting of major hepatectomy. Primary goal of ALPPS is to obtain a faster increase in FLR compared to conventional portal vein occlusion obtained either surgically or radiologically, thus allowing an early hepatectomy avoiding the risk of tumor progression and exclusion from surgery. A review of studies published until now in the literature is represented in Table 4. In both, all series from the literature and present one, the rate of program completion was 100 %, meaning that no patient dropped out after the first operation. It should be underlined that further studies on larger series are needed to confirm that no chance of exclusion from second step of ALPPS may occur. So far, we still prefer to avoid prudentially to take any ‘‘one-way’’ solution during the first operation (e.g. placement of a plastic bag or tapes to be removed surgically) since the possibility of a drop out
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HCC
Right hepatectomy
7 ALPPS
Observative descriptive
Results
10 patients
15 PVE
Alvarez et al. [21]
N
CLM
10
Morbidity: 53 %
NCLM
3
Mortality: 0 %
Intrahepatic cholangiocarcinoma
3
Program conclusion 100 %
Klatskin
3
CLM
3
Mortality: 2 patients
cannot be excluded and the patient would then need a further surgical procedure even when not resectable. In this series, two drop-out patients were recorded at the moment of the first laparotomy, maybe reflecting that the pool of candidates to ALPPS is represented by borderline resectable patients and therefore the risk of unresectable disease (both hepatic and extrahepatic) is consistent. Schnitzbauer et al. described the first series of 25 cases completed in five centers in Germany; the study shows a FLR percentage increase of 74 % in 9 days, then faster and more effective compared to what normally occurs with vascular occlusion techniques alone [10]. Ideal candidates would thus be patients with a very small FLR (\20 %), who are not expected to achieve an adequate rate of hypertrophy with traditional techniques: the dramatic effect on liver regeneration is explained as a consequence of the interruption of collateral vessels between the two portions of parenchyma, which amplifies the effect of portal flux to FLR, hindering the
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recanalization of embolized portal branches. The parenchyma to be resected, in the interval between surgical steps, works as an auxiliary liver until its removal, once the FLR has reached an appropriate volume [9]. Knoefel et al. [20] compared the rate of parenchymal hypertrophy in a series of 22 patients undergoing isolated PVE (12 patients), ALPPS (7 patients) or the combination of the two procedures (3 patients) and reported a mean volume increase by 63 % after 3 days in patients undergoing ALPPS (volume gain of 22 % per day), significantly higher than the group treated with PVE alone. In addition, in patients who experience insufficient parenchymal growth after PVE, the ALPPS approach can still be evaluated as an option to convert them to resectability [20]. In the present study, as already reported in other literature series [10, 16, 19–21], the parenchymal transection carried out together with portal vein occlusion seems to give a benefit in terms of hypertrophy rate, especially if compared with a previous series of PVE from our institution which recorded a mean volumetric increase of 50.3 % [5]. Even the issue of tumoral progression in the interval between PVE and surgery, particularly evident in the nonembolized liver as demonstrated by Kokudo et al. [23], is partly obviated by ALPPS approach, as the interval before the curative resection is considerably reduced. Another reason to emphasize the value of this approach is the avoidance of FLR infiltration by the tumor, especially when located in the shelter of major vascular structures which should therefore be sacrificed in case of infiltration or encasement. The main drawback of this approach is the high rate of morbidity and mortality reported in the literature: Schnitzbauer [10] reported a morbidity of 64 % and a mortality rate of 12 %, while Knoefel [20] reported that only two out of 7 patients had a course free of complications. In the first period of the present series all patients developed postoperative complications, especially related to septic events secondary to ischemic necrosis of the liver segment IV, deprived of both vascular arterial and portal inflow. In order to prevent these complications, Andriani proposed the removal of the IV segment during the first surgical step [24]. Indeed, a patient in the present series developed segment IV necrosis and finally died for sepsis in spite of an intermediate surgical step for segment IV resection. Anyway, at the moment, series indicating the results of this additional procedure are still lacking in the literature. ALPPS technique should not be proposed with the aim of a complete replacement of traditional portal occlusion techniques, but with the main goal of expansion of the pool of candidates to surgery, rescuing those patients who are not supposed to be able to undergo surgical clearance of the liver after conventional techniques (PVE, PVL) either for inadequate FLR or tumor progression: in this setting,
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expected morbidity and mortality should be reappraised, taking into account that ALPPS corresponds to extreme hepatic surgery, associated with a rate of complication significantly higher compared to conventional major hepatic surgery. In the first period of this study indeed, indications to ALPPS procedure were considered: (1) severely inadequate FLR (\20 %) (2) need for surgical exploration for resectability assessment (as in locally advanced tumors or neoplasms infiltrating the hilum) (3) intraoperative findings consistent with more advanced disease compared to preoperative staging (4) high risk of rapid progression of disease. In our institution, as reported in first series [22], ALPPS approach was therefore initially considered suitable for the treatment of patients affected by Klatskin tumors who require, despite a small tumor volume, extended hepatectomies associated with surgery of the biliary tract: the analysis of this first series of patients has led to a reevaluation of the indication to this strategy, as a consequence of encountered criticisms. Relevant morbidity reported in Series 1 of this study was mainly related to complications secondary to ischemic necrosis and abscess of segment IV, deprived of both arterial and venous vascularization, in patient who had experienced prolonged cholestasis due to biliary tree infiltration by the tumor. Indeed both these conditions (segment IV devascularization and cholestasis) represent risk factors for postoperative adverse events. Li et al. in a recent series of ALPPS found that patients requiring biliary drainage for biliary strictures had an higher risk of infections and bile leak compared to others, concluding that patients with Klatskin tumors have additional risk factors for intraabdominal infection and bacteraemia so that cholestatic liver with lower regeneration potential have been considered by these authors a contraindication to ALPPS [22]. These facts, along with the considerations of Aloia who defines ALPPS ‘‘all touch technique’’ [25], opposed to the ‘‘no-touch’’ described by Neuhaus et al. [26], (due to intraoperative manipulation of portobiliary hilar structures and need of leaving in place the neoplasm after the first surgical step), led to a shift in ALPPS indication, as regards both the type of intervention and the treated pathology. In Series 2 indeed, candidates to ALPPS were patients requiring right hepatectomy for CLM (no need for segment IV resection in patients without prolonged cholestasis). ALPPS procedure, performed in this setting, seems to be safe and feasible in a selected population of patients, allowing obtaining of an acceptable rate of morbidity and mortality. In the current practice of our Institution, ALPPS indications are the following for CLM: (1) two-stage
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hepatectomy, (2) liver metastases surgery combined with colorectal cancer resection (FLR \20 % when healthy liver; FLR \30 % if CALI-chemotherapy associated liver injury), (3) intraoperative finding of bilobar lesions, without possibility of clearance in a single step. In the present series, the issue regarding the difference between volume increase and functional reserve gain has not been specifically addressed: despite this, it should be postulated that signs of PLF in patients undergoing ALPPS and experiencing adequate volume increase are related to a still insufficient and/or impaired parenchymal functional reserve. This phenomenon is similar to what reported in patients undergoing liver transplantation and developing small for size syndrome, when portal hyperafflux causes both a functional and structural damage to liver parenchyma [27, 28]. In conclusion, ALPPS approach allows to expand the number of candidates to surgical treatment thanks to the possibility of achieving an higher rate of hypertrophy in a shorter time compared to traditional techniques of vascular occlusion. The high rate of morbidity and mortality related to biliary and septic complications leads to a shift in indications toward patients with liver metastases from colorectal cancer who require right hepatectomy. Conflict of interest
None.
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