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Otsuka et al.                                                                                                                                   Indications and technique for LLR in HCC with liver cirrhosis

           (LLR), a minimally invasive treatment for liver cancer, is   centers  in  resecting  HCC.  In  Western  countries,
           now increasingly performed worldwide.  However, few   treatment is driven by the Barcelona Clinic Liver Cancer
                                             [11]
           studies have investigated LLR for HCC patients with liver   algorithm, [22,23]  in which evidence of portal hypertension
           cirrhosis, and its applicability for this population is thus   is a contraindication for surgical resection. Clinically
           unclear. This review describes the indications for LLR in   relevant portal hypertension is defined as the presence
           this patient subgroup and offers guidance on appropriate   of esophageal varices or splenomegaly associated with a
           surgical technique.                                platelet count lower than 100 × 10⁹/L. [22]

           CURRENT STATUS OF LLR IN THE                       In East Asian countries, the best candidates for resection
           TREATMENT OF HCC                                   are identified by using indocyanine green retention rate
                                                              as part of a detailed assessment of preoperative hepatic
           LLR was initially described by Reich et al.  Subsequent   functional reserve. [24,25]  Additionally, use of volumetric
                                              [12]
           studies showed that it offered minimal invasiveness with   computed tomography for assessment of remnant liver
           no reduction in safety or disease curability for primary and   volume  after resection  is as important  as estimation
                                                                                         [26]
           metastatic liver tumors in selected patients. [13,14]  However,   of hepatic functional  reserve.  Therefore,  patients
           because  of  the  technical  difficulty  of  this  procedure,   with signs of  portal hypertension can be candidates
           it  was  not  performed  until  the 1990s.  Development   for resection  if they receive  adequate  perioperative
           of  surgical  devices  and  technical  refinements  in  the   management,  e.g.  endoscopic  treatment  of  esophageal
           early 2000s increased surgical interest. In the First   varices to minimize risk of rupture and pre-hepatectomy
                                                                                                            [21]
           International  Consensus   Conference   (Louisville  or concomitant splenectomy to improve hypersplenism.
           Consensus), convened in 2008, LLR was described as   Anatomic resection, which can remove the tumor-bearing
           a safe and effective surgical approach for management   portal territory, is preferred from an oncological perspective
                                                                                     [24]
           of liver disease when performed by trained surgeons   for radical treatment of HCC.  Outcomes of liver resection
           with experience in both hepatobiliary and laparoscopic   for patients with HCC and cirrhosis has been dramatically
                                                                                                       [21]
           surgery.  In addition, a small number of studies reported   improved with parenchyma-preserving technique.
                  [15]
           that LLR was useful for cirrhotic patients. [16,17]  With the   Percutaneous ablation therapies are another treatment
           subsequent uptake of LLR, the Second International   of choice for small nodular  HCC in patients with
           Consensus Conference on LLR, held in 2014, concluded   cirrhosis located deep inside the liver; however, such
           that minor LLRs, which were performed for left lateral   treatment is not suitable for superficially located HCC,
           sectionectomies  or resections of anterior and  lateral   because of  the  increased risk  of  bleeding,   tumor
                                                                                                      [27]
           segments (Couinaud’s segments II, III, IVb, V, and VI),   seeding,  and thermal injury to adjacent organs.
                                                                                                            [29]
                                                                      [28]
           had become standard practice.  Despite encouraging   Therefore, surgical resection might be the ideal option
                                       [11]
           findings from high-volume centers, [18,19]  the efficacy of LLR   for superficial small HCCs.
           for patients with cirrhosis remains inconclusive because
           of the low sample sizes of published studies. The most   Patient selection for LLR
           recent meta-analysis indicated that the benefits of LLR   The selection of candidates for LLR is the most important
           would lead to expansion of its indications to include HCC   consideration in safely performing LLR. With respect to
           with chronic liver disease. [20]                   host factors, an LLR candidate should have liver function
                                                              sufficient for the same procedure performed as open liver
           SURGICAL INDICATIONS                               resection.  With  respect  to  tumor  factors,  the  classical
                                                              indications for LLR are that the tumor should have a
           Resection of HCC in patient with liver cirrhosis   diameter less than 5 cm and be located in areas with
           In  patients with HCC with liver cirrhosis, careful   easy technical access to laparoscopy, i.e. in the left lateral
           selection  of surgical  candidates is essential  in order   section (Couinaud’s segments II and III) or on the surface
           to avoid treatment-related  complications,  e.g. liver   of the inferior region of the liver (Couinaud’s segments
           failure. Because of differences in the characteristics of   IVb, V, and VI).
           cirrhosis between Asian and Western countries, there
           is considerable  variability regarding the  indications   Partial liver resection or left lateral sectionectomy are the
           for  HCC resection.  Therefore, surgical indications   typical procedures for such tumors. With accumulating
           for HCC associated with portal hypertension  remain   experience and technical advancement, LLR has been
           controversial.  Surgery  is contraindicated  for patients   performed for tumors larger than 5 cm and for lesions
           with encephalopathy, uncontrollable  ascites, or   located in the posterior-to-superior region of the liver
           jaundice (serum total bilirubin level > 2.0 mg/dL). [21]  (Couinaud’s segments VII, VIII,  and  IVa), including
                                                              advanced non-anatomical  and anatomical LLR such
           Asian centers have been more aggressive than Western   as major hepatectomy (involving the abovementioned
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