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World J Gastroenterol. Nov 28, 2026; 32(44): 120736
Published online Nov 28, 2026. doi: 10.3748/wjg.120736
Portal vein-based subsegmental classification of liver segment four for parenchyma-sparing laparoscopic resection: A retrospective study
Kun Huang, Department of General Surgery, Mianyang Hospital of Traditional Chinese Medicine, Mianyang 621000, Sichuan Province, China
Hai-Yang Hu, Kai Chen, Xing-Yu Chen, Zhu Chen, Yu Sun, Cheng-You Du, Gui-Xiong Chang, Hao Fu, Cong Hu, Heng Xiao, Xiang Lan, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400000, China
ORCID number: Kun Huang (0000-0002-3369-9749); Kai Chen (0000-0003-1083-073X); Heng Xiao (0000-0002-8384-4027); Xiang Lan (0000-0002-5626-0106).
Co-first authors: Kun Huang and Hai-Yang Hu.
Co-corresponding authors: Heng Xiao and Xiang Lan.
Author contributions: Lan X and Xiao H designed the research study, revised the manuscript critically for important intellectual content and supervised the study and they contribute equally to this study as co-corresponding authors; Huang K and Hu HY developed the methodology and they contribute equally to this study as co-first authors; Chen K, Chen XY and Chen Z performed the investigation; Sun Y, Du CY, Chang GX, Fu H and Hu C collected and curated the data; Huang K performed the visualization and drafted the manuscript; and all authors have read and approved the final manuscript.
Supported by the 2024 University-Hospital Joint Innovation Fund of Chengdu University of Traditional Chinese Medicine, No. LH202402010.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (Approval No. 2025-460-01).
Informed consent statement: The requirement for informed consent was waived by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University due to the retrospective nature of the study.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. Because the study involves patient imaging data and institutional operative records, restrictions apply to their public availability due to ethical and privacy considerations.
Corresponding author: Xiang Lan, PhD, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Youyi Road, Yuzhong District, Chongqing 400000, China. lanxiang_tmmu@163.com
Received: March 10, 2026
Revised: April 8, 2026
Accepted: May 20, 2026
Published online: November 28, 2026
Processing time: 207 Days and 12.9 Hours

Abstract
BACKGROUND

Conventional cranial-caudal classification of hepatic segment 4 (S4) based on the falciform ligament does not fully reflect individual variation in portal inflow and may limit anatomical precision during parenchyma-sparing liver resection.

AIM

To characterize portal inflow variation in S4, develop a portal vein-based subsegmental classification, and assess its surgical applicability in laparoscopic parenchyma-sparing liver resection.

METHODS

This retrospective single-center study included 207 patients who underwent laparoscopic liver resection (LLR) between June 2021 and April 2024. Preoperative contrast-enhanced computed tomography, magnetic resonance imaging, and three-dimensional reconstruction were performed to define the portal inflow patterns of S4. Classification-guided laparoscopic parenchyma-sparing resection was assessed using intraoperative indocyanine green fluorescence. Detailed perioperative biochemical and pathological analyses focused on the type II subgroup. Exploratory comparative follow-up analysis was performed using Kaplan-Meier estimation and the log-rank test.

RESULTS

Intermediate branches crossing the falciform ligament were identified in 192 of 207 patients (92.8%). S4 was classified as type I (cranial-caudal, 120/207, 58.0%), type II (left-right, 78/207, 37.7%), or type III (scattered, 9/207, 4.3%). In the type II subgroup, postoperative liver enzymes increased transiently and recovered by postoperative day 5, and all analyzed patients achieved negative pathological margins. In the comparative follow-up dataset, the pathological distribution included 113 hepatocellular carcinomas, 38 colorectal liver metastases, 36 intrahepatic cholangiocarcinomas, and 20 benign lesions. During follow-up, 32 patients developed recurrence, and 5 died. The median follow-up duration was 22.0 (interquartile range: 17.0-27.0) months. Exploratory Kaplan-Meier analysis revealed no significant difference in overall survival (OS) or progression-free survival (PFS) between the novel and conventional groups (log-rank P = 0.22 and 0.21, respectively).

CONCLUSION

A portal vein-based classification of S4 may improve anatomical understanding and support individualized parenchyma-sparing LLR. The current data support anatomical plausibility and technical feasibility, while exploratory comparative analysis showed no significant difference in OS or PFS. Formal validation and broader long-term assessments remain necessary.

Key Words: Liver segment 4; Portal vein anatomy; Subsegmental classification; Laparoscopic liver resection; Parenchyma-sparing surgery; Glissonean pedicle; Indocyanine green fluorescence

Core Tip: This study proposes a portal vein-based subsegmental classification of liver segment 4 (S4) derived from preoperative imaging and three-dimensional reconstruction. Intermediate branches crossing the falciform ligament were frequently identified, suggesting that the conventional boundary of S4 may not fully reflect its true portal territory. The proposed framework may support individualized parenchyma-sparing laparoscopic resection, particularly for type II anatomy. In the exploratory comparative follow-up dataset, no significant difference in overall survival or progression-free survival was observed between the novel and conventional groups. Formal validation remains necessary.



INTRODUCTION

Traditionally, segment 4 (S4) is defined as the region between the Cantlie line and the falciform ligament and is further subdivided into S4a (cranial portion) and S4b (caudal portion) based on the distribution of Glissonean pedicles[1,2]. Although widely accepted, this classification often fails to account for individual anatomical variations. As a result, it may lead to unnecessary resection of functional liver parenchyma or to an increased risk of positive surgical margins, thereby limiting its applicability in precision hepatic surgery[3-5].

However, conventional descriptions of S4 mainly emphasize the cranial-caudal subdivision into S4a and S4b and do not adequately address portal inflow patterns that extend across the falciform ligament. In particular, intermediate branches (IBs) arising between the Glissonean pedicles of segment 3 (G3) and Glissonean pedicles of segment 4 (G4) have not been sufficiently incorporated into the practical anatomical framework of S4. From a surgical perspective, these branches are clinically important because they may delineate perfused parenchyma beyond the traditional falciform ligament-based boundary, thereby influencing the extent of resection required to achieve adequate margins while preserving uninvolved liver tissue.

In this study, we sought to achieve three objectives. First, we aimed to characterize the portal inflow anatomy of S4, with particular attention given to IBs crossing the falciform ligament. Second, we aimed to develop a portal vein-based subsegmental classification of S4 that better reflects individual perfusion territories than the conventional falciform ligament-based model. Third, we aimed to explore the surgical applicability of this classification in laparoscopic parenchyma-sparing liver resection guided by preoperative three-dimensional (3D) reconstruction and intraoperative indocyanine green fluorescence.

MATERIALS AND METHODS
Study aims and patient selection

The primary aim of this retrospective study was to characterize the portal inflow anatomy of S4 and determine the anatomical significance of IBs crossing the falciform ligament. The secondary aim was to establish a portal vein-based subsegmental classification of S4. The third aim was to explore the clinical applicability of this classification in laparoscopic parenchyma-sparing liver resection.

This was a retrospective, single-center study conducted at the First Affiliated Hospital of Chongqing Medical University. A total of 207 consecutive patients who underwent laparoscopic liver resection (LLR) between June 2021 and April 2024 were included. All patients underwent complete preoperative imaging, including contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), and 3D reconstruction. This study was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (Approval No. 2025-460-01). The requirement for informed consent was waived due to the retrospective nature of the study.

Imaging protocol

All patients underwent multiphasic contrast-enhanced CT or gadolinium-enhanced MRI with thin-slice acquisition (≤ 1 mm). CT scans included arterial, portal venous, and delayed phases and were obtained with a multidetector scanner (Revolution CT, GE Healthcare, United States). MRI was performed on a 3.0 Tesla system (MAGNETOM Skyra, Siemens Healthineers, Germany) with hepatobiliary phase imaging after the administration of Gd-EOB-DTPA. DICOM data from the portal venous phase were imported into either the Hisense CAS system (Hisense Medical Technology, Qingdao, China) or Amira 3D software (Thermo Fisher Scientific, United States). Imaging evaluation and S4 classification were independently performed by two experienced researchers (Huang K and Xiao H). In cases of disagreement regarding the classification of S4, a third researcher (Lan X) was consulted. Final decisions were made through group discussion, using a majority-rule approach. Formal interobserver agreement statistics, such as, Cohen’s kappa were not prospectively planned or systematically recorded in this retrospective study and therefore were not reported.

Surgical technique

All procedures were performed laparoscopically by experienced hepatobiliary surgeons. After induction of general anesthesia, patients were placed in a dorsal-elevated supine position with the right side slightly elevated. A five-trocar approach was generally used, with the trocar placement adjusted according to the tumor location and the planned transection plane. Intraoperative ultrasonography was routinely performed to confirm the tumor location, vascular relationships, and intended resection territory. Hepatic inflow occlusion was applied selectively using the intermittent Pringle manoeuvre when necessary. Liver parenchymal transection was performed using ultrasonic energy devices, with clips or sutures used for vascular and biliary control as appropriate. For classification-guided resection, the target Glissonean pedicle(s) of S4 were identified according to preoperative 3D reconstruction and intraoperative ultrasonography. Depending on the anatomical subtype, selective control of the relevant pedicle(s) was achieved to define the intended resection territory. Intraoperative indocyanine green (ICG) fluorescence imaging was then used to visualize portal territory demarcation and guide anatomical parenchymal transection. In the extended S4 resection, the umbilical fissure vein served as an important posterior landmark. This strategy enables individualized parenchyma-sparing resection while preserving uninvolved liver tissue whenever oncologically appropriate.

Data collection and statistical analysis

Clinical, pathological, and follow-up data were retrospectively extracted from electronic medical records and the comparator follow-up dataset. Continuous variables are reported as the mean ± SD or median with interquartile range, as appropriate. Categorical variables are presented as n (%). Repeated-measures analysis of variance was used for perioperative biochemical trends in the type II subgroup. Exploratory survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. All analyses were performed using R software (version 4.3.3).

Assessment of perioperative liver function and the resection margin

Perioperative liver function parameters-including aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, prothrombin time [international normalized ratio (INR)], albumin, and albumin-bilirubin (ALBI) score-were measured preoperatively and on postoperative days (PODs) 1, 3, and 5. All values were expressed as the mean ± SD.

Repeated-measures analysis of variance (ANOVA) was applied to evaluate overall temporal changes in these parameters across all time points, followed by Bonferroni-corrected paired t tests comparing each postoperative value with the preoperative baseline to assess short-term hepatic recovery.

Pathological resection margins were defined as the shortest distance from the tumor edge to the transection plane. Two independent pathologists reviewed all the specimens, and discrepancies were resolved by consensus. R0 resection was defined as a microscopically tumor-free margin ≥ 1 mm, in accordance with the international consensus for hepatobiliary malignancies.

The fluorescence-pathology concordance rate, defined as the proportion of cases in which intraoperative ICG fluorescence demarcation coincided with the histopathological tumor margin, was calculated for all patients. The mean resection margin distance and concordance rate were recorded to evaluate anatomical accuracy and oncologic safety.

These parameters were analyzed to assess short-term biochemical recovery and pathological margin status in type II resections guided by the proposed S4 classification.

Subgroup selection and exploratory follow-up analysis

All 207 patients were included in the anatomical mapping and subtype classification analyses. Detailed perioperative biochemical and pathological analyses focused on the type II subgroup because this pattern most clearly reflected the incremental surgical relevance of the proposed classification beyond the conventional cranial-caudal S4a/S4b model. Specifically, the left-right portal inflow pattern of type II directly supports lateralized parenchyma-sparing resection. In contrast, type I largely overlaps with the traditional cranial-caudal concept, whereas type III was infrequent and anatomically heterogeneous, limiting meaningful subgroup outcome analysis. Pathology composition and follow-up outcomes were additionally assessed using the available comparator dataset. In this dataset, patients were categorized into novel and conventional groups according to the recorded surgical strategy. Overall survival (OS) was defined as the interval from surgery to death from any cause or the last follow-up. Progression-free survival (PFS) was defined as the interval from surgery to recurrence, progression, death, or last follow-up, whichever occurred first. Because the comparator grouping was closely associated with the anatomical subtype, these analyses were considered exploratory.

RESULTS
Patient characteristics

A total of 207 patients were enrolled in this study. The mean age was 58.2 ± 11.0 (range: 27.0-91.0) years, and 140 (67.6%) were male. All patients underwent LLR and had complete preoperative imaging data, including reconstruction of the Glissonean pedicles.

Novel anatomical discovery

Redefining S4 boundaries and clinical applications: IBs arising from the bifurcation of the G3 and G4, which supplied a narrow area on both sides of the falciform ligament, were identified in 192 patients (92.8%). If these branches are considered part of G4, then the anatomical left boundary of S4 should be redefined as extending to the left of the falciform ligament (Figure 1). Specifically, 102 patients (49.3%) had one IB, 81 (39.1%) had two, and 9 (4.3%) had 3. Only 15 patients (7.2%) had no identifiable IBs. In a representative patient, the tumor was located near the falciform ligament within S4 and the anterior-ventral segment. In accordance with the conventional anatomical classification, left hemihepatectomy combined with resection of the anterior-ventral segment would have been needed to achieve negative surgical margins. However, when the new concept of S4 incorporating IBs was applied, laparoscopic sparing liver resection of the S4 and anterior-ventral segments was sufficient to achieve safe margins (Figure 2 and Video 1).

Figure 1
Figure 1 Portal territory-defined boundaries of segment 4 based on intermediate branches. A-D: Axial contrast-enhanced computed tomography images showing intermediate branches (IBs; orange arrows) arising between the Glissonean pedicles of segments 3 and 4, supplying liver parenchyma on both sides of the falciform ligament; E and F: Three-dimensional reconstruction images demonstrating bilateral perfusion territories of the IBs, extending across the falciform ligament; G: Intraoperative laparoscopic view confirming the presence of IB during hepatic dissection; H: Schematic illustration of the traditional anatomical segment 4 (S4) boundary, with the left margin defined by the falciform ligament; I: Portal territory-based redefinition of the S4 territory showing leftward extension beyond the falciform ligament, in line with IB perfusion; J: Refined anatomical boundary of S4 according to the proposed portal vein-based classification, encompassing the full extent of perfused parenchyma. IB: Intermediate branch; G2: Glissonean pedicles of segment 2; G3: Glissonean pedicles of segment 3; G4: Glissonean pedicles of segment 4.
Figure 2
Figure 2 Portal territory-guided anatomical resection of extended segment 4. A and B: Axial contrast-enhanced computed tomography images showing a lesion abutting the falciform ligament (orange arrows), a location that would typically require left hemihepatectomy under conventional anatomical definitions; C and D: Intraoperative laparoscopic views identifying two intermediate branches (IBs; IB1 and IB2) arising between the Glissonean pedicles of segments 3 and 4, supplying the parenchyma lateral to the falciform ligament; E: Indocyanine green (ICG) fluorescence negative staining delineating the extended segment 4 territory, corresponding to the perfusion zones of IB1 and IB2; F: Parenchymal transection guided by ICG staining and anatomical landmarks preserving segments 2 and 3, while achieving a negative surgical margin (R0). The umbilical fissure vein serves as a reference for the posterior limit of resection. IB: Intermediate branch; G3: Glissonean pedicles of segment 3; G4: Glissonean pedicles of segment 4; S2: Segment 2; S3: Segment 3; S4: Segment 4; ES4: Extended segment 4; UFV: Umbilical fissure vein serves.

S4 subtypes and surgical applications: While classical segmentation divides S4 into cranial (S4a) and caudal (S4b) subsegments, our findings demonstrate that this cephalocaudal pattern is not consistently observed among patients. A substantial proportion of patients exhibited a left-right portal inflow pattern across the falciform ligament, indicating the need for a more comprehensive system. On the basis of portal vein anatomy, we developed a three-type classification scheme (Table 1 and Figures 3, 4, 5, 6, 7, and 8).

Figure 3
Figure 3 Type Ia classification: Bilateral cranial-caudal trunk type of segment 4. A-D: Axial contrast-enhanced computed tomography images from a representative type Ia case, showing two dominant Glissonean trunks-Glissonean pedicles of segment 4 (G4; G4a and G4b)-supplying the cranial and caudal subsegments of segment 4 (S4), respectively. Two intermediate branches (IBs; IB1 and IB2) are also visible in panel A, arising near the bifurcation of segment 3 and S4; E: Three-dimensional portal vein reconstruction highlighting the bifurcated G4a and G4b pedicles supplying distinct cranial and caudal territories of S4; F: Schematic diagram illustrating the spatial distribution of G4a, G4b, and IBs, reinforcing the concept of bilateral cranial-caudal trunk anatomy in type Ia cases. IB: Intermediate branch; G4: Glissonean pedicles of segment 4.
Figure 4
Figure 4 Type Ib classification: Unilateral cranial trunk with contralateral caudal dispersion in segment 4. A-C: Gadolinium-enhanced magnetic resonance imaging images from a representative type Ib case. A dominant Glissonean pedicle (Glissonean pedicles of segment 4a) supplies the cranial portion of segment 4, while the caudal portion (Glissonean pedicles of segment 4b) receives scattered inflow from multiple smaller branches, indicating perfusion asymmetry; D: Three-dimensional reconstruction showing unilateral cranial inflow and contralateral caudal dispersion, with one intermediate branch arising near the bifurcation zone; E: Schematic diagram illustrating the type Ib pattern, with centralized cranial inflow and diffuse caudal distribution, reinforcing the concept of asymmetric cephalocaudal perfusion in this subtype. IB: Intermediate branch; G4: Glissonean pedicles of segment 4.
Figure 5
Figure 5 Type Ic classification: Fully dispersed Glissonean branching pattern in segment 4. A-C: Axial contrast-enhanced computed tomography images from a representative type Ic case, showing fine and scattered Glissonean branches (Glissonean pedicles of segments 4a and 4b) supplying cranial and caudal subsegments without a dominant trunk; D: Three-dimensional portal vein reconstruction confirming a dispersed origin of multiple small Glissonean pedicles, each individually supplying subregions of segment 4 (S4); E: Schematic diagram illustrating the cranial-caudal perfusion pattern of S4 in type Ic, characterized by multiple independently arising Glissonean branches rather than a single dominant pedicle. G4: Glissonean pedicles of segment 4.
Figure 6
Figure 6 Type IIa classification: Bilateral trunk-type left-right subdivision of segment 4. A and B: Axial contrast-enhanced computed tomography images from a representative type IIa case, showing two dominant Glissonean pedicles-Glissonean pedicles of segment 4 L (S4 L) and Glissonean pedicles of segment 4R (S4R)-supplying the left and right subsegments of S4 L and S4R, respectively; C: Three-dimensional portal vein reconstruction confirming a bilateral trunk-type configuration, with independent inflow to S4 L and S4R; D: Schematic diagram illustrating the symmetric left-right portal supply pattern, supporting lateralized subsegmental resection while preserving non-involved liver parenchyma. IB: Intermediate branch; G2: Glissonean pedicles of segment 2; G3: Glissonean pedicles of segment 3; G4: Glissonean pedicles of segment 4.
Figure 7
Figure 7 Type IIb classification: Unilateral trunk with contralateral dispersion in left-right subdivision of segment 4. A-C: Axial contrast-enhanced computed tomography images from a representative type IIb case. A dominant Glissonean pedicles of segment 4 (G4; G4R) supplies the right subsegment of segment 4 (S4; S4R), while the left subsegment (S4 L) receives multiple fine and scattered branches (G4 L), without a dominant trunk; D: Three-dimensional portal vein reconstruction confirming the asymmetric left-right perfusion pattern, with a single structured G4R pedicle and dispersed G4 L branches; E: Schematic diagram illustrating the type IIb anatomy, characterized by unilateral trunk-type inflow to S4R and contralateral scattered inflow to S4 L. G4: Glissonean pedicles of segment 4.
Figure 8
Figure 8 Type III classification: Scattered Glissonean inflow without dominant trunk anatomy in segment 4. A and B: Axial contrast-enhanced computed tomography images from a representative type III case, showing multiple small Glissonean branches entering segment 4 (S4) from varying directions, with no discernible cranial-caudal or left-right segmentation pattern; C: Three-dimensional portal vein reconstruction revealing a disorganized inflow configuration, composed of scattered pedicles and intermediate branches supplying overlapping territories within S4; D: Schematic diagram illustrating the non-converging, diffuse vascular distribution in type III, which lacks structured segmentation and requires intraoperative fluorescence guidance for accurate subsegmental resection. IB: Intermediate branch; G4: Glissonean pedicles of segment 4.
Table 1 Portal vein-based classification of segment 4 (n = 207), n (%).

Overall (n = 207)
New S4 classification subtypes
Type I (cranial-caudal subdivision)120 (58.0)
    Ia (bilateral trunk type, Figure 3)    55 (26.6)
    Ib (unilateral trunk type, Figure 4)    20 (9.7)
    Ic (dispersed branching, Figure 5)    45 (21.7)
Type II (left-right subdivision)78 (37.7)
    IIa (bilateral trunk type, Figure 6)    27 (13.0)
    IIb (unilateral trunk type, Figure 7)    51 (24.6)
Type III (scattered pattern, Figure 8)9 (4.3)

From a surgical perspective, each subtype carries distinct surgical implications. Type I resection generally remained compatible with cranial-caudal subsegmental resection along the conventional S4a/S4b orientation, although branching variability still required individualized planning. Type II represented the most clinically distinctive pattern because its left-right portal inflow configuration directly supported lateralized parenchyma-sparing resection of the left and right subsegments of S4 (S4 L and S4R). In contrast, type III resection was uncommon and anatomically heterogeneous, and surgical planning in this subgroup relied mainly on individualized ICG fluorescence mapping rather than on a fixed pedicle-based resection plane. Because type II most clearly demonstrated the incremental surgical relevance of the proposed classification beyond the conventional cranial-caudal framework, detailed perioperative biochemical and pathological analyses were subsequently focused on this subgroup. A representative case (Figure 9 and Video 2) underscores the clinical utility of the new classification. The tumor was located at the junction of S4 and the anterior portion of segment 5, overlapping the right side of S4 and approaching the falciform ligament. Under traditional anatomical segmentation, resection would require the removal of the entire S4 and part of the right anterior section to ensure negative margins. However, preoperative 3D imaging revealed this case as type IIb, with a dominant right S4 pedicle (G4R) and scattered left S4 branches (G4 L). This anatomy enabled precise resection of segment 5 and S4R alone, preserving the uninvolved S4 L parenchyma while achieving adequate oncological margins. The resection line was guided by Glissonean control and confirmed by ICG fluorescence, demonstrating the value of portal-based segmentation in optimizing parenchyma-sparing liver surgery.

Figure 9
Figure 9 Portal-based subsegmental resection of segment 4 L and segment 4R guided by Glissonean anatomy and indocyanine green fluorescence demarcation. A and B: Axial contrast-enhanced computed tomography images demonstrating separate inflow from the Glissonean pedicles of segment 4 (G4; G4 L and G4R) pedicles to the left and right of segment 4 (S4; S4 L and S4F) subsegments of S4, respectively (orange arrows); C: Three-dimensional portal vein reconstruction confirming a bilateral trunk-type configuration supplying S4 L and S4R; D and E: Intraoperative views showing identification and isolation of the G4R pedicle using the Glissonean approach; F: Surface marking of the liver based on anatomical landmarks delineating the boundary between S4 L and S4R; G-I: Indocyanine green fluorescence negative staining revealing distinct perfusion territories of S4 L and S4R, enabling precise subsegmental resection with functional parenchymal preservation and negative margins (R0). See Video 2 for operative details. S4: Segment 4; G4: Glissonean pedicles of segment 4.
Short-term liver function and resection margin outcomes of type II resection

The perioperative changes in liver function and resection margin parameters among type II patients are summarized in Table 2. Repeated-measures ANOVA demonstrated significant time-dependent changes in AST, ALT, total bilirubin, INR, albumin, and ALBI scores (all P value < 0.001).

Table 2 Perioperative liver function and resection margins in type II patients (n = 78).
Variable
Pre-operative
POD1
POD3
POD5
P value
AST (U/L)31.5 ± 10.6239.1 ± 81.576.3 ± 37.743.6 ± 15.8< 0.001
ALT (U/L)28.3 ± 8.4192.8 ± 77.670.3 ± 29.839.8 ± 12.2< 0.001
Total bilirubin (µmol/L)12.9 ± 4.120.8 ± 7.225.6 ± 7.215.8 ± 4.8< 0.001
INR1.00 ± 0.101.21 ± 0.101.18 ± 0.091.05 ± 0.050.002
Albumin (g/L)42.0 ± 4.135.6 ± 4.236.9 ± 3.939.3 ± 3.40.004
ALBI score-2.67 ± 0.33-1.98 ± 0.41-2.12 ± 0.37-2.45 ± 0.32< 0.001
Resection margin (mm)---9.8 ± 3.2-
R0 resection rate (%)---100 (78/78)-

AST and ALT levels peaked on POD1 (239.1 ± 81.5 U/L and 192.8 ± 77.6 U/L, respectively) and returned near baseline by POD5 (43.6 ± 15.8 U/L and 39.8 ± 12.2 U/L, respectively; all P > 0.05 vs preoperative), indicating transient hepatocellular injury with rapid recovery. The total bilirubin concentration peaked on POD3 (25.6 ± 7.2 μmol/L) and declined thereafter, whereas the prothrombin time (INR) showed mild, reversible prolongation on POD1-3. Albumin levels decreased transiently but recovered toward baseline by POD5.

The mean pathological resection margin was 9.8 ± 3.2 mm, and R0 resection was achieved in all patients (100%, 78/78). The fluorescence-pathology concordance rate was 97.4% (76/78), confirming precise anatomical alignment between portal-based ICG demarcation and histologic margins.

Collectively, these findings indicate mild, reversible postoperative biochemical disturbance together with negative pathological margins and precise anatomical targeting achieved through classification-guided type II resection.

Exploratory follow-up outcomes in the comparator dataset

The comparator follow-up dataset included 207 patients, of whom 78 were assigned to the Novel group and 129 to the Conventional group. Pathology revealed 113 hepatocellular carcinomas, 38 colorectal liver metastases, 36 intrahepatic cholangiocarcinomas, and 20 benign lesions. During follow-up, 32 patients developed recurrence, and 5 died. The median follow-up duration was 22.0 (interquartile range: 17.0-27.0) months.

Exploratory Kaplan-Meier analysis showed no significant difference in OS or PFS between the novel and conventional groups (Figure 10; log-rank P = 0.22 for OS and P = 0.21 for PFS). These findings suggest that the classification-guided strategy did not show an apparent adverse effect on medium-term oncologic outcomes in this retrospective comparator dataset.

Figure 10
Figure 10  Exploratory Kaplan-Meier survival analysis in the comparator dataset. A: Overall survival in the conventional and novel groups. No statistically significant difference was observed (log-rank P = 0.22); B: Progression-free survival in the conventional and novel groups. No statistically significant difference was observed (log-rank P = 0.21). Numbers at risk (number censored) are presented below each curve. Given that the comparator grouping was closely linked to anatomical subtype rather than an independent treatment strategy, these analyses should be interpreted as exploratory.
DISCUSSION

A central finding of the present study is that IBs crossing the falciform ligament were identified in the vast majority of patients. This observation suggests that IBs are not rare incidental variants but rather a frequently overlooked component of S4 portal inflow anatomy. Classical descriptions of the medial segment have long emphasized the cranial-caudal subdivision into S4a and S4b and have treated the falciform ligament as a practical boundary. However, previous anatomical and imaging studies have also shown that the vascularization of S4 is substantially more variable than this traditional framework suggests[2,4,6]. In this context, our findings support portal territory-based reinterpretation of S4 anatomy and help explain why a falciform ligament-based definition may be insufficient for precision parenchyma-sparing resection in selected patients.

Building on these anatomical observations, we proposed a portal vein-based subsegmental classification of S4 with three major patterns: Type I (cranial-caudal), type II (left-right), and type III (scattered). From a surgical perspective, the greatest incremental value lies in type II anatomy because its left-right inflow configuration directly supports lateralized resection of S4 L or S4R beyond the conventional S4a/S4b concept. This point is clinically relevant because prior laparoscopic S4 resection techniques have largely been developed within the traditional cranial-caudal framework[7], whereas fluorescence-guided portal territory identification has increasingly shown value in defining functional segmental boundaries when the pedicle anatomy is fine, variable, or difficult to reproduce intraoperatively[8,9]. Accordingly, the proposed classification system should be understood not merely as an anatomical description but also as a practical framework linking preoperative 3D planning with intraoperative territory confirmation.

From a perioperative perspective, the analyzed type II cases showed transient postoperative biochemical disturbance with recovery by POD5, together with negative pathological margins in all analyzed cases. These findings support the technical feasibility and favorable short-term biochemical recovery of classification-guided type II resection. Moreover, they should not be overinterpreted. Hepatectomy is a complex metabolic and regenerative event, and the trajectories of AST or ALT alone cannot fully represent postoperative liver function. Therefore, although the current results are clinically reassuring, they are more appropriately interpreted as supporting technical applicability than as definitive evidence of broader functional preservation.

From an oncologic perspective, the present findings also require cautious interpretation. In the comparator dataset, exploratory Kaplan-Meier analysis showed no significant difference in OS or PFS between the Novel and Conventional groups. This direction is consistent with findings reported in certain disease-specific settings, particularly those involving colorectal liver metastases, in which parenchyma-sparing and anatomic strategies may achieve comparable long-term oncologic outcomes in appropriately selected patients[10,11]. However, the disease-specific literature is not uniform. In hepatocellular carcinoma, some meta-analyses have favored anatomic resection for long-term survival or recurrence outcomes[12,13]. For this reason, the present exploratory comparative analysis should not be interpreted as proof of oncologic equivalence. Rather, it suggests that, within this mixed-pathology retrospective dataset, the proposed classification-guided strategy did not show an obvious adverse signal for medium-term survival outcomes.

Several limitations should be acknowledged. First, this was a retrospective single-center study subject to inherent selection bias. Second, although all 207 patients contributed to anatomical mapping and classification, detailed perioperative biochemical and pathological analyses focused on the type II subgroup, which limits direct extrapolation to type I and type III patterns. Third, formal reproducibility testing of the proposed classification was not performed because interobserver agreement statistics such as Cohen’s kappa were not prospectively recorded. Fourth, the comparative analysis was exploratory: The novel group corresponded to type II anatomy, whereas the conventional group consisted predominantly of type I and type III cases; therefore, the anatomical subtype and operative grouping were not independent. Finally, the comparator dataset included mixed pathology and only a small number of death events, which constrains the strength of long-term oncologic inference. Taken together, these considerations suggest that the proposed framework is best viewed as an anatomically plausible and technically useful model that now requires broader external validation, more granular perioperative assessments, and longer disease-specific follow-up.

CONCLUSION

A portal vein-based subsegmental classification of S4 improves the anatomical understanding of portal inflow variation and may assist individualized parenchyma-sparing liver resection. The present findings support anatomical plausibility and technical feasibility, while exploratory comparative analysis revealed no significant difference in OS or PFS. Formal reproducibility testing, broader perioperative assessments, and longer-term validation remain necessary.

ACKNOWLEDGEMENTS

We would like to thank the radiology and surgical teams at the First Affiliated Hospital of Chongqing Medical University for their invaluable support in data collection and imaging analysis.

References
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Footnotes

Peer review: Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Gastroenterology and hepatology

Country of origin: China

Peer-review report’s classification

Scientific quality: Grade B, Grade B, Grade B, Grade C

Novelty: Grade A, Grade A, Grade A, Grade B

Creativity or innovation: Grade A, Grade B, Grade B, Grade C

Scientific significance: Grade B, Grade C, Grade C, Grade C

P-Reviewer: Sarangi Y, Assistant Professor, Associate Faculty, Consultant, India; Shelat VG, Associate Professor, Singapore; Shukla A, Assistant Professor, India S-Editor: Lin C L-Editor: A P-Editor: Zhang YL

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