Title: Preoperative Albumin-Bilirubin Grade Combined with Sarcopenia Predicts Long-term
Outcomes after Laparoscopic Gastrectomy for Advanced Gastric Cancer
Version: 1 Date: 18 Jun 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-Retrospective Design and Selection Bias
Although the study is multicenter, it remains retrospective, inherently limiting causal inference
and introducing potential selection bias. Confounding variables might not have been fully
adjusted, particularly those unmeasured or missing from the dataset.
-Ethnic and Regional Homogeneity
The study population is exclusively Chinese. While valuable for regional clinical guidance,
this limits the external validity and generalizability of the findings to non-Asian or multiethnic
cohorts, especially given the differing body compositions and sarcopenia thresholds across
populations.
-Lack of External Validation Beyond Two Centers
Both centers involved are within the same national context, potentially sharing clinical practices
and patient characteristics. A broader external validation set from more diverse geographic or
institutional settings would strengthen the predictive generalizability of the s-ALBI index.
-Omission of Confounding Nutritional and Inflammatory Factors
Factors such as C-reactive protein (CRP), prealbumin, body mass index (BMI), or nutritional
screening scores (e.g., PG-SGA or MUST) were not included. These could confound or mediate
the observed relationships, particularly when interpreting sarcopenia and ALBI scores.
-No Comparative Analysis with Existing Prognostic Tools
While the s-ALBI index is compared to ALBI and sarcopenia alone, it is not directly compared
to other preoperative risk models (e.g., PNI, GNRI, CONUT, or systemic inflammatory markers
like NLR or PLR), which limits the reader’s ability to gauge the relative clinical utility of s-
ALBI.
-Subjective or Undetailed Chemotherapy Adjustment Criteria
The description of postoperative chemotherapy protocols includes “adjusted based on drug side
effects or tumor response,” which lacks standardization. Variability in chemotherapy regimens
and adherence may affect survival outcomes, introducing another confounding factor.
-Potential Variability in Sarcopenia Assessment
Although a single radiologist performed the CT-based muscle measurements, interobserver and
intraobserver reliability were not addressed. Sarcopenia classification thresholds may also not
be universally accepted or applicable to other populations.
-Inconsistent Definition of Endpoints Across Literature
The study defines recurrence-free survival (RFS) in a composite manner, including death from
any cause. This may not align with standard RFS definitions, which often exclude non-cancer-
related deaths, potentially diluting oncologic-specific predictive value.
-Limited Time Frame for Imaging and Laboratory Data Collection
CT scans and biochemical tests are restricted to within one month and one week preoperatively,
respectively. Any perioperative changes in nutritional or hepatic status are not captured and
could influence the actual preoperative risk profile.
-No Investigation into Postoperative Changes in ALBI or Muscle Mass
The study exclusively focuses on preoperative variables. However, serial postoperative changes
in ALBI or sarcopenia status (e.g., muscle loss during chemotherapy) may also impact long-
term outcomes and are not explored.
-Unexplored Mechanistic Basis for s-ALBI Prognostic Value
While several plausible biological explanations are offered (e.g., inflammatory responses,
myokine secretion), the mechanistic pathways linking ALBI and sarcopenia to poor prognosis
are speculative and not supported by biomarker or molecular data.
Title: Preoperative Albumin-Bilirubin Grade Combined with Sarcopenia Predicts Long-term
Outcomes after Laparoscopic Gastrectomy for Advanced Gastric Cancer
Version: 1 Date: 18 Jun 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-Retrospective Design and Selection Bias
Although the study is multicenter, it remains retrospective, inherently limiting causal inference
and introducing potential selection bias. Confounding variables might not have been fully
adjusted, particularly those unmeasured or missing from the dataset.
-Ethnic and Regional Homogeneity
The study population is exclusively Chinese. While valuable for regional clinical guidance,
this limits the external validity and generalizability of the findings to non-Asian or multiethnic
cohorts, especially given the differing body compositions and sarcopenia thresholds across
populations.
-Lack of External Validation Beyond Two Centers
Both centers involved are within the same national context, potentially sharing clinical practices
and patient characteristics. A broader external validation set from more diverse geographic or
institutional settings would strengthen the predictive generalizability of the s-ALBI index.
-Omission of Confounding Nutritional and Inflammatory Factors
Factors such as C-reactive protein (CRP), prealbumin, body mass index (BMI), or nutritional
screening scores (e.g., PG-SGA or MUST) were not included. These could confound or mediate
the observed relationships, particularly when interpreting sarcopenia and ALBI scores.
-No Comparative Analysis with Existing Prognostic Tools
While the s-ALBI index is compared to ALBI and sarcopenia alone, it is not directly compared
to other preoperative risk models (e.g., PNI, GNRI, CONUT, or systemic inflammatory markers
like NLR or PLR), which limits the reader’s ability to gauge the relative clinical utility of s-
ALBI.
-Subjective or Undetailed Chemotherapy Adjustment Criteria
The description of postoperative chemotherapy protocols includes “adjusted based on drug side
effects or tumor response,” which lacks standardization. Variability in chemotherapy regimens
and adherence may affect survival outcomes, introducing another confounding factor.
-Potential Variability in Sarcopenia Assessment
Although a single radiologist performed the CT-based muscle measurements, interobserver and
intraobserver reliability were not addressed. Sarcopenia classification thresholds may also not
be universally accepted or applicable to other populations.
-Inconsistent Definition of Endpoints Across Literature
The study defines recurrence-free survival (RFS) in a composite manner, including death from
any cause. This may not align with standard RFS definitions, which often exclude non-cancer-
related deaths, potentially diluting oncologic-specific predictive value.
-Limited Time Frame for Imaging and Laboratory Data Collection
CT scans and biochemical tests are restricted to within one month and one week preoperatively,
respectively. Any perioperative changes in nutritional or hepatic status are not captured and
could influence the actual preoperative risk profile.
-No Investigation into Postoperative Changes in ALBI or Muscle Mass
The study exclusively focuses on preoperative variables. However, serial postoperative changes
in ALBI or sarcopenia status (e.g., muscle loss during chemotherapy) may also impact long-
term outcomes and are not explored.
-Unexplored Mechanistic Basis for s-ALBI Prognostic Value
While several plausible biological explanations are offered (e.g., inflammatory responses,
myokine secretion), the mechanistic pathways linking ALBI and sarcopenia to poor prognosis
are speculative and not supported by biomarker or molecular data.
Please review this paper.
user
Title: Preoperative Albumin-Bilirubin Grade Combined with Sarcopenia Predicts Long-term
Outcomes after Laparoscopic Gastrectomy for Advanced Gastric Cancer
Version: 1 Date: 18 Jun 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-Retrospective Design and Selection Bias
Although the study is multicenter, it remains retrospective, inherently limiting causal inference
and introducing potential selection bias. Confounding variables might not have been fully
adjusted, particularly those unmeasured or missing from the dataset.
-Ethnic and Regional Homogeneity
The study population is exclusively Chinese. While valuable for regional clinical guidance,
this limits the external validity and generalizability of the findings to non-Asian or multiethnic
cohorts, especially given the differing body compositions and sarcopenia thresholds across
populations.
-Lack of External Validation Beyond Two Centers
Both centers involved are within the same national context, potentially sharing clinical practices
and patient characteristics. A broader external validation set from more diverse geographic or
institutional settings would strengthen the predictive generalizability of the s-ALBI index.
-Omission of Confounding Nutritional and Inflammatory Factors
Factors such as C-reactive protein (CRP), prealbumin, body mass index (BMI), or nutritional
screening scores (e.g., PG-SGA or MUST) were not included. These could confound or mediate
the observed relationships, particularly when interpreting sarcopenia and ALBI scores.
-No Comparative Analysis with Existing Prognostic Tools
While the s-ALBI index is compared to ALBI and sarcopenia alone, it is not directly compared
to other preoperative risk models (e.g., PNI, GNRI, CONUT, or systemic inflammatory markers
like NLR or PLR), which limits the reader’s ability to gauge the relative clinical utility of s-
ALBI.
-Subjective or Undetailed Chemotherapy Adjustment Criteria
The description of postoperative chemotherapy protocols includes “adjusted based on drug side
effects or tumor response,” which lacks standardization. Variability in chemotherapy regimens
and adherence may affect survival outcomes, introducing another confounding factor.
-Potential Variability in Sarcopenia Assessment
Although a single radiologist performed the CT-based muscle measurements, interobserver and
intraobserver reliability were not addressed. Sarcopenia classification thresholds may also not
be universally accepted or applicable to other populations.
-Inconsistent Definition of Endpoints Across Literature
The study defines recurrence-free survival (RFS) in a composite manner, including death from
any cause. This may not align with standard RFS definitions, which often exclude non-cancer-
related deaths, potentially diluting oncologic-specific predictive value.
-Limited Time Frame for Imaging and Laboratory Data Collection
CT scans and biochemical tests are restricted to within one month and one week preoperatively,
respectively. Any perioperative changes in nutritional or hepatic status are not captured and
could influence the actual preoperative risk profile.
-No Investigation into Postoperative Changes in ALBI or Muscle Mass
The study exclusively focuses on preoperative variables. However, serial postoperative changes
in ALBI or sarcopenia status (e.g., muscle loss during chemotherapy) may also impact long-
term outcomes and are not explored.
-Unexplored Mechanistic Basis for s-ALBI Prognostic Value
While several plausible biological explanations are offered (e.g., inflammatory responses,
myokine secretion), the mechanistic pathways linking ALBI and sarcopenia to poor prognosis
are speculative and not supported by biomarker or molecular data.
assistant