00227359

June 08, 2026, 09:00

Reader’s expertise on the topic of the manuscript

Does the reader have a conflict of interest?

The overall quality of the manuscript, based on the above-listed criteria, should be evaluated and classified according to the following five categories

Language quality (style, grammar, and spelling) should be evaluated and classified according to the following five categories.

Clarifying Survival Estimates After Adrenal Metastasectomy Following Liver Transplantation for Hepatocellular Carcinoma Manuscript type: Letters to the Editor Running title: Survival after adrenal metastasectomy Author: Cuneyt Kayaalp Institution: Cuneyt Kayaalp, Department of Surgery, Istanbul Atlas University, Istanbul, Türkiye ORCID number: 0000-0003-4657-2998 Corresponding author: Cuneyt Kayaalp, MD, Department of Surgery, Istanbul Atlas University, Istanbul, Türkiye. [cuneytkayaalp@gmail.com] Author contributions: Kayaalp C conceived and wrote the letter; the author has read and approved the final manuscript. Supported by: None. Conflict-of-interest statement: Kayaalp C is the only author of the study included in the systematic review discussed in this letter; the author declares no financial conflict of interest related to this manuscript. Data sharing statement: No additional data are available. Abstract Ramia et al. reviewed isolated adrenal metastasis of hepatocellular carcinoma after liver transplantation. Their work is clinically relevant, but the survival analysis requires clearer methodology. In rare conditions reported mainly as case reports, publication bias may favor favorable surgical outcomes. Moreover, a survival curve that includes only a subset of patients, mixes surgical and non-surgical treatments, and omits censoring marks may overstate the precision of the estimate. Additional transplant cases from Ha et al., Abdel Wahab et al., and Agrawal et al. may be eligible for incorporation into an updated patient-level analysis. A revised curve restricted to adrenalectomy-treated patients, with explicit censoring and transparent extraction assumptions, would improve the interpretation of survival after adrenal metastasectomy. Key Words: Hepatocellular carcinoma; Liver transplantation; Adrenal metastasis; Adrenalectomy; Survival analysis; Kaplan-Meier analysis; Publication bias; Metastasectomy Core Tip This letter comments on the survival curve in a systematic review of adrenal metastasis of hepatocellular carcinoma after liver transplantation. The main concern is that survival estimates may be affected by publication bias, treatment heterogeneity, incomplete inclusion of eligible cases, and the absence of censoring marks. A revised patient-level Kaplan-Meier analysis restricted to surgically treated patients, incorporating additional eligible reports and explicit censoring, would provide a more transparent estimate of survival after adrenal metastasectomy. TO THE EDITOR I read with great interest the systematic review and case report by Ramia et al. on adrenal metastasis of hepatocellular carcinoma after liver transplantation[1]. I am a co-author of one of the studies included in that review. The authors should be congratulated for addressing a rare and clinically relevant pattern of post-transplant recurrence and for emphasizing that selected patients with isolated adrenal recurrence may benefit from surgical treatment. However, I would like to raise several methodological concerns regarding the survival analysis. In systematic reviews based mainly on case reports, favorable outcomes are more likely to be written, submitted, and accepted for publication. This may introduce publication bias and lead to reported clinical outcomes that are better than those observed in routine practice. This limitation should be explicitly acknowledged. One way to reduce this risk is to include small case series in addition to single-case reports and to use the largest extractable patient-level dataset whenever possible. Although the review included 21 patients, the survival curve appears to include only a limited subset of those cases. Thus, the outcomes of the remaining patients are not fully represented in the graph or the accompanying text. Contacting the authors of the original reports to obtain missing follow-up data would be another scientifically sound method to reduce missingness and improve the accuracy of survival estimates. Treatment heterogeneity is another issue. If the purpose of the survival analysis is to estimate outcomes after adrenal metastasis resection, patients treated with radiotherapy rather than adrenalectomy should either be excluded or analyzed separately. A sensitivity analysis restricted to adrenalectomy-treated patients would provide a more homogeneous estimate of survival after surgical treatment. The seven patients in the series by Ha et al. are particularly relevant because this study included liver transplant recipients who underwent adrenalectomy for metachronous adrenal metastasis, and its published survival graph contains censoring information[2]. If individual patient data are not directly available, these data may still be incorporated into an updated analysis using transparent digitization methods, provided that the extraction method and assumptions are clearly stated. In addition, potentially eligible reports published within the review search period appear to be absent from the final table. Abdel Wahab et al. reported a solitary adrenal recurrence of hepatocellular carcinoma five years after living donor liver transplantation, treated successfully by adrenalectomy[3]. Similarly, Agrawal et al. reported isolated adrenal recurrence after liver transplantation treated with adrenalectomy, with the patient remaining recurrence-free at 3 years of follow-up[4]. These cases appear compatible with the clinical scope of the review and should either be included in an updated analysis or have their exclusion justified. Incorporating these additional cases, together with the surgical cases from Ha et al., would allow construction of an updated survival curve composed only of patients treated with adrenalectomy. Such an analysis may nearly double the number of surgically treated patients represented in the current curve and would provide a more clinically interpretable estimate of survival after adrenal metastasectomy. These comments do not diminish the clinical value of the review. Rather, they underscore that the survival benefit in such a rare clinical setting should be interpreted cautiously and supported by the most complete and methodologically consistent dataset available. In conclusion, adrenalectomy remains a reasonable option in carefully selected liver transplant recipients with isolated adrenal metastasis from hepatocellular carcinoma. However, a revised survival analysis restricted to surgically treated patients and the inclusion of all eligible published cases would improve the reliability and transparency of the reported survival outcomes. References 1 Ramia JM Franco M, Alcázar C, Carbonell-Morote S, Rubio-García JJ, Rodríguez M, Pascual S, Melgar P, Villodre Tudela C. Adrenal metastasis of hepatocellular carcinoma after liver transplantation: Case report and systematic review of literature. World J Transplant 2026; 16: 116999 [DOI: 10.5500/wjt.v16.i2.116999] 2 Ha TY Hwang S, Ahn CS, Kim KH, Lee YJ, Moon DB, Song GW, Jung DH, Park GC, Lee SG. Resection of metachronous adrenal metastasis after liver resection and transplantation for hepatocellular carcinoma. Dig Surg 2014; 31: 428-435 [PMID: 25573138 DOI: 10.1159/000370078] 3 Abdel Wahab M Shehta A, Ibrahim EM, Eldesoky RT, Sultan AA, Zalata KR, Fathy O, Shiha U. Adrenalectomy for solitary recurrent hepatocellular carcinoma five years after living donor liver transplantation: A case report. Int J Surg Case Rep 2019; 54: 23-27 [PMID: 30513494 PMCID: PMC6279994 DOI: 10.1016/j.ijscr.2018.11.062] 4 Agrawal J Kumar P, Arora A, Kumar A. Isolated adrenal metastasis of hepatocellular carcinoma post liver transplantation: A rare entity. Clinical Case Studies and Reports 2021; 4: 1-3 [DOI: 10.15761/CCSR.1000166] Footnotes Specialty type: Transplantation Country/Territory of origin: Türkiye Peer-review model: Externally peer reviewed, if accepted for peer review by the journal. Open-Access statement: This article is an open-access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, if accepted and published by Baishideng Publishing Group Inc.