Challenges and controversies of laparoscopic hepatectomy in the era of conversion therapy for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is insidious in onset and rapidly progressive, more than half of patients are initially diagnosed with unresectable HCC (uHCC) and thus lose the opportunity for radical surgery. Conversion therapy centered on targeted therapy, immunotherapy, and combination with local regional treatments can achieve tumor downstaging and improvement of liver function in some patients with uHCC, thereby rendering them eligible for curative resection. Laparoscopic hepatectomy, with its advantages of minimal invasiveness, precision, reduced surgical stress, and rapid recovery, is progressively becoming the preferred surgical approach for patients who successfully undergo conversion. However, compared with primarily resectable HCC, conversion therapy induces hepatic and perihepatic tissue inflammation, fibrosis, and adhesions, increases the fragility of liver parenchyma and critical ductal structures, obliterates anatomical planes, blurs tumor margins, and causes fluctuations in hepatic functional reserve. These changes significantly escalate the technical difficulty of laparoscopic surgery and markedly increase the risks of complications such as bleeding, bile leakage, and liver failure. Moreover, challenges posed by the heterogeneity of tumor biological behavior, unclear optimal timing of surgery, and controversies regarding oncological efficacy further complicate the clinical application of sequential laparoscopic hepatectomy. The authors systematically summarize the unique technical challenges, perioperative risk management, and patient selection dilemmas associated with sequential laparoscopic hepatectomy after conversion therapy for uHCC, drawing upon the latest domestic and international guidelines, evidence‑based medical evidence, and clinical research advances. They also discuss controversial issues and optimization strategies for this refined surgical treatment strategy, and offer perspectives on future directions, with the aim of providing a reference for standardizing the clinical application of this procedure and improving curative outcomes for patients with intermediate-advanced HCC.