First Left Hepatic Trisectionectomy Including Segment One with New Associated Liver Partition and Portal Vein Ligation with Staged Hepatectomy (ALPPS) Modification: How To Do It?

Background

The most important barrier in achieving of R0 resection after a major hepatectomy is often the failure to preserve a sufficient future liver remnant (FLR) and avoiding postoperative liver failure (PLF). Associated Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a novel technique for the surgical removal of extensive liver tumors, which were previously considered unresectable. This procedure regularly achieves a rapid increase in the volume of the left lateral segments (FLR), often within 1 week after surgery.

However, this procedure is controversial due to its high morbidity and mortality. Since the milestone multicenter study led by Dr. Schlitt was published [1], about 200 papers have followed, thereby establishing an ALPPS procedure registry [2]. In the long history of liver surgery, ALPPS is similar to a little child – it simply requires more time to develop.

As a result, many modifications for ALPPS and selection criteria have been introduced to help decrease the morbidity and mortality of this procedure [3–6]. The benefits of ALPPS are rapid hypertrophy of the FLR, feasibility, and a high rate of R0 resection. Well-recognized weaknesses of ALPPS are morbidity, death, and early tumor recurrence.

ALPPS has given hepatobiliary surgeons the ability to help patients with seemingly hopeless extensive liver tumors, whether primary or metastatic, especially those with colorectal liver metastases (CRLM) in the face of a small-for-size FLR.

Here, we describe a new modification of the ALPPS procedure, carrying out an extended left hepatectomy, including segment one, in a 36-year-old woman with synchronic CRLM.

Case Report

STEP 2 PROCEDURE::

Modified ALPPS was performed in accordance with the previously mentioned surgical steps (Figure 3). The patient was hemodynamically stable during both operations and she received 6 unites of red packed cell and 8 fresh frozen plasma units during the first operation. During the first operation, the FLR appeared bluish, soft, and vulnerable. This intraoperative condition of the liver confirmed our preoperative concerns about the quality of the FLR.

The patient was observed in an intensive care unit. On day 7, a volumetric liver CT scan showed an increase in the size of the right posterior sector (Segment 6+7), about 100% (1190 cm2) larger than its original size. The FLR/BW ratio increased to 1.3%. The standard FLR increased to 0.47% (Figure 4). During the inter-stage phase, there were no signs of complications such as an infection or a bile leak. The patient was subsequently taken to the operating room and the extended left hepatic trisectionectomy with left colectomy was completed during step 2.

Initially, her postoperative course was uneventful and there were no signs of post-hepatectomy liver failure according to the 50–50 criteria. However, the patient experienced a severe abdominal infection with Acinetobacter, causing sepsis on postoperative day 8 after the second surgical step. The infection was treated and controlled with the proper sensitive antibiotics.

She received Tigecycline and the infection was controlled, but bilirubin increased dramatically. We stopped Tigecycline and started Colistin, the only remaining sensitive antibiotic.

Unfortunately, the patient developed acute renal injury with uremic pericarditis due to Colistin toxicity, which required 3 sessions of dialysis by our nephrology team. The renal function recovered completely within days. The right-sided pleural effusion was treated with ultrasound (US)- guided aspiration. At the same time, bile leak or duct narrowing was ruled out by endoscopic retrograde cholangiopancreatography (ERCP) and a CT scan revealed normal condition (Figure 5).

Liver enzymes and coagulation parameters were normalized within 5 days; the bilirubin was elevated for 8 weeks postoperatively, from day 8 after the second step procedure, related to the severe sepsis and the adverse effect of Tigecycline. Subsequently, the patient recovered slowly, and reintroduction of ambulation and oral feeding was prolonged. Later on, the patient received Xeloda 1500 mg twice daily as adjuvant chemotherapy.

Postoperatively, hepatectomy and colectomy specimens underwent a standard pathological work-up. Histology findings showed colon cancer and liver metastases with free margins, tumor stage pT3, N0, M1, R0, G2. Synchronous liver biopsy taken from the FLR showed regenerative parenchyma with broadening of the trabecular liver cells, fatty degeneration of about 30%, and elevated proliferative activity estimated at 10%, with Ki67-positive nuclear reaction of regenerating hepatocytes.

Discussion

Up to 50% of patients with colorectal cancer (CRC) simultaneously show liver metastases. The only existing therapy that improves survival in patients with colorectal liver metastases is surgical resection.

Nowadays, liver resection is considered a curative approach to obtain better survival rates in patients with colorectal cancer liver metastases. Especially, patients with synchronic CRLM must be assessed by a hepatobiliary multidisciplinary board, which must include an experienced liver surgeon, since early surgical presentation for patients with potentially resectable colorectal cancer liver metastases is paramount for overall survival and highlights the importance of a preoperative multimodality evaluation. Inconsistencies between the ideas of oncologists and hepatic surgeons regarding respectability and its underutilization may lead to worse patient survival [9].

If the primary CRC is without obstruction symptoms, “liver surgery first” can be performed. When CRLM is unresectable, the target of preoperative chemotherapy is to downstage the liver mass to allow resection. After chemotherapy, hepatic resection must be recommended to patients with optimal response after neo-adjuvant chemotherapy [10].

Neo-adjuvant chemotherapy with FOLFOX4 plus bevacizumab is well tolerated and has a positive response rate leading to curative surgery, which suggests an excellent survival advantage in previously unresectable CRC with simultaneous meta-static metastases [11].

The main obstacle in achieving an R0 resection after major hepatectomy is the inability to preserve an adequate future liver remnant to avoid post-hepatectomy liver failure, associated liver partition and portal vein ligation with staged hepatectomy (ALPPS). This is a novel technique for the resection of tumors previously considered unresectable [12].

ALPPS has evolved into various modified forms. Machado et al. performed laparoscopy during the first stage of the procedure. They indicated that laparoscopic ALPPS might prevent rigid adhesions, allowing an easier second stage. Later on, many institutions around the world performed laparoscopic ALPPS and several procedures were demonstrated in the recent literature [13–17].

Gauzolino et al. described 3 additional types of the “classic” ALPPS procedure. Similar to the original ALPPS procedure, these modified types permit surgical removal of hepatic tumors that were originally considered unresectable. Nevertheless, the efficiency and safety of these modified approaches cannot be evaluated at present due to a lack of detailed data [18–20].

Hepatobiliary surgeons in Hong Kong first reported the use of an anterior approach in ALPPS in 2 patients. Later, Ardiles et al. showed that 37% of the patients in the International ALPPS Registry experienced liver resection using an anterior approach during the first stage of ALPPS [21,22].

Li et al. developed a no-touch technique to treat tumor infiltration of the right portal vein or biliary bifurcation as part of ALPPS, and Robles et al. in Spain described a new modified form of the ALPPS procedure, which they termed associating liver tourniquet and portal ligation with staged hepatectomy [23,24].

In general, the aim of these techniques is to eliminate all metastases in the future liver remnant, which has insufficient volume to maintain the liver functionality and induce hypertrophy [25].

Our case is the first in which ligation of the right anterior portal pedicle was attempted, in order to allow the posterior sector of the right liver lobe for hypertrophy to produce sufficient future liver size. The feasibility and the technical steps in this case were attempted and carried out with the basic principles of the originally described ALPPS.

The location and extent of liver metastatic deposits dictates the location and the extent of liver resection. An overall predominance of right hepatic lobe metastases has been documented, independent of site of the primary colorectal carcinoma [26]. Hence, most ALPPS were described with the associated ligation of the right portal vein, in our case where our patient had an extensive left liver lobe metastatic deposits including liver segments 5 and 8. She was a candidate for associated ligation of the right anterior pedicle (RAP) of the portal vein with preserving and allowing liver segment 6 and 7 hypertrophy as a future liver remnant.

We anticipated that an increasing portal inflow through ligation of the RAP itself with the in situ resection is sufficient to induce appropriate hypertrophy; therefore, we deliberately omitted ligation of the left portal vein and decided to ligate only the RAP. As expected, the hypertrophy outcome of segment 6 and 7 was adequate after 7 days, resulting in 100% volume increase of FLR.

Although the right hepatic vein branches to segments 5 and 8 were occluded during the first step, congestion of liver segments 5 and 8 did not occur, due to the existing venous drainage via middle hepatic vein branches.

Long-term outcomes of classical ALPPS at this time exist presently for CRLM. Taking the high rate of recurrences into consideration, our patient underwent routine systemic conversion chemotherapy with radiological and tumor marker response. Furthermore, the performed preoperative systemic conversion chemotherapy also serves us as an excellent selection parameter to carry on with the modified ALPPS.

In summary, specific variations in the technical aspects of the ALPPS procedure exist in different surgical centers worldwide. Our modified ALPPS was feasible, with satisfactory a 6-month short-term result, and without any signs of recurrence. It induces adequate liver hypertrophy and at the same time it can offer the possibility of a cure to patients with tumors previously declared unresectable, especially when the classical ALPPS for whatever reason is not applicable.

Conclusions

Despite the severe postoperative medical complications, left hepatic trisectionectomy with the new modified ALPPS technique appears to be surgically applicable and promising. Further investigations are required, especially in regard to proper selection of patients.