Outcomes of Salvage Surgery for Initially Unresectable Hepatocellular Carcinoma Converted by Transcatheter Arterial Chemoembolization Combined with Lenvatinib plus Anti-PD-1 Antibodies: A Multicenter Retrospective Study.

Introduction: The actual rate of conversion surgery and its prognostic advantages remain unclear. This study aimed to assess the outcomes of salvage surgery after conversion therapy with triple therapy (transcatheter arterial chemoembolization [TACE] combined with lenvatinib plus anti-PD-1 antibodies) in patients with initially unresectable hepatocellular carcinoma (uHCC). Methods: Patients with initially uHCC who received at least one cycle of first-line triple therapy and salvage surgery at five major cancer centers in China were included. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) rates after salvage surgery. The secondary endpoints were perioperative complications, 90-day mortality, and pathological tumor response. Results: Between June 2018 and December 2021, 70 patients diagnosed with uHCC who underwent triple therapy and salvage surgery were analyzed: 39 with Barcelona Clinic Liver Cancer (BCLC) stage C, 22 with BCLC stage B, and 9 with BCLC stage A disease. The median interval between the start of triple therapy and salvage surgery was 4.3 months (range, 1.7-14.2 months). Pathological complete response and major pathological response were observed in 29 (41.4%) and 59 (84.3%) patients, respectively. There were 2 cases of perioperative mortality (4.3%) and 5 cases of severe perioperative complications (7.1%). With a median follow-up of 12.9 months after surgery (range, 0.3-36.8 months), the median OS and RFS were not reached. The 1- and 2-year OS rates were 97.1% and 94.4%, respectively, and the corresponding RFS rates were 68.9% and 54.4%, respectively. Conclusion: First-line combination of TACE, lenvatinib, and anti-PD-1 antibodies provides a better chance of conversion therapy in patients with initially uHCC. Furthermore, salvage surgery after conversion therapy is effective and safe and has the potential to provide excellent long-term survival benefits.

Aberrant regulation of autophagy disturbs fibrotic liver regeneration after partial hepatectomy.

Reports indicate that autophagy is essential for maintaining hepatocyte proliferative capacity during liver regeneration. However, the role of autophagy in fibrotic liver regeneration is incompletely elucidated. We investigated the deregulation of autophagic activities in liver regeneration after partial hepatectomy using a CCl4-induced fibrosis mouse model. The baseline autophagic activity was significantly increased in the fibrotic liver. After 50% partial hepatectomy (PHx), liver regeneration was remarkably decreased, accompanied by increased hepatocyte size and binuclearity ratio. Moreover, the expression of autophagy-related proteins was functionally deregulated and resulted in a reduction in the number of autophagosome and autophagosome-lysosome fusions. We further showed upregulation of autophagy activities through verapamil administration, improved hepatocyte proliferation capacity, and restricted cellular hypertrophy and binuclearity ratio. In conclusion, we demonstrated that the impairment of liver regeneration is associated with aberrant autophagy in fibrotic liver and that enhancing autophagy with verapamil may partially restore the impaired liver regeneration following PHx.

Impact of Bile Duct Tumor Thrombus on the Long-Term Surgical Outcomes of Hepatocellular Carcinoma Patients: A Propensity Score Matching Analysis.

BACKGROUND: Hepatectomy with tumor thrombectomy is the preferred treatment option for hepatocellular carcinoma (HCC) patients with bile duct tumor thrombus (BDTT); however, the impact of BDTT on their prognosis is unclear. OBJECTIVE: We aimed to investigate the long-term surgical outcomes of HCC patients with BDTT. METHODS: The data of HCC patients with and without BDTT who underwent hepatectomy were retrospectively reviewed and the long-term outcomes were compared. For propensity score matching (PSM) analysis, patients were matched in a 1:1 ratio. Subgroup analysis was conducted according to the American Joint Committee on Cancer (AJCC) staging system. RESULTS: Before PSM, HCC patients with BDTT had more advanced tumor stages and adverse clinicopathological features. Recurrence-free survival (RFS) and overall survival (OS) were significantly higher in the non-BDTT group before PSM (RFS, p < 0.001; OS, p < 0.001), while after PSM, the BDTT group had significantly poorer RFS (p = 0.025). There was no difference in OS between the groups (p = 0.588). Subgroup analysis showed that RFS and OS in AJCC stage I-II patients were significantly poorer in the BDTT group; no differences were found in the AJCC stage III group before or after PSM. When the presence of BDTT was recommended to increase the AJCC staging system by one stage in AJCC stage I-II patients, the predictive ability for RFS and OS was higher. CONCLUSIONS: BDTT was associated with significantly poorer long-term surgical outcomes in AJCC stage I-II patients. A modified AJCC staging system including BDTT status in stage I-II might have a better prognostic ability.

Imaging Features of Hepatocellular Carcinoma With Bile Duct Tumor Thrombus: A Multicenter Study.

OBJECTIVES: There are still challenging problems in diagnosis of hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) before operation. This study aimed to analyze the imaging features of HCC with B1-B3 BDTT. MATERIALS AND METHODS: The clinicopathological data and imaging findings of 30 HCC patients with B1-B3 BDTT from three high-volume institutions were retrospectively reviewed. A total of 631 patients without BDTT who were randomly collected from each of the enrolled centers were recorded as the control group to analyze the differences in clinicopathological characteristics and imaging features between the two groups. A total of 453 HCC patients who underwent surgical treatment in the three institutions from January 2020 to December 2020 were collected for a blinded reading test as the validation group. RESULTS: HCC patients with B1-B3 BDTT had more advanced tumor stages and adverse clinicopathological features. HCC lesions were detected in all patients, and intrahepatic bile duct dilation was observed in 28 (93.3%) patients with B1-B3 BDTT and 9 (1.43%) patients in HCC without BDTT. The intrahepatic bile duct dilation showed no enhancement at hepatic arterial phase (HAP) and no progressively delayed enhancement at portal venous phase (PVP), but it was more obvious at PVP on CT. In the reports of the 30 HCC patients with B1-B3 BDTT generated for the image when the scan was done, BDTT was observed in all 13 B3 patients and 3 of 12 B2 patients, but none of the 5 B1 patients. Fourteen patients were misdiagnosed before surgery. However, when using intrahepatic bile duct dilation in HCC patients as a potential biomarker for BDTT diagnosis, the sensitivity and specificity for BDTT diagnosis were 93.33% and 98.57%, respectively. The blinded reading test showed that intrahepatic bile duct dilation in CT and MRI scans could be for separating HCC patients with B1-B3 BDTT from HCC patients without BDTT. CONCLUSIONS: The HCC lesions and intrahepatic bile duct dilation on CT or MRI scans are imaging features of HCC with BDTT, which might facilitate the early diagnosis of B1-B3 BDTT.

Lenvatinib Combined with Anti-PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study.

BACKGROUND: Lenvatinib (LEN) combined with anti-PD-1 antibodies (PD-1) exerted promising effects on unresectable hepatocellular carcinoma (uHCC). We assessed the safety and clinical efficacy of triple therapy [LEN+PD-1+transcatheter arterial chemoembolization (TACE)] in uHCC. METHODS: uHCC patients with an ECOG PS score of 0-1 and Child-Pugh class A who underwent triple therapy were included. The primary endpoint was objective response rate (ORR) based on mRECIST. Secondary endpoints were conversion rate to liver resection and treatment-related adverse events. RESULTS: Between November 2018 and December 2020, 62 uHCC patients who underwent triple therapy at four major cancer centers in China were analyzed, including 35 in BCLC-C, 21 in BCLC-B, and 6 in BCLC-A. With a median follow-up of 12.2 months (range, 7.6-33.3 months), the investigator and blinded independent central review-assessed ORR were 80.6% and 77.4%, respectively. A total of 33 patients (53.2%) reached the standard of conversion to resectable HCC and 29 patients underwent resection. The median interval between start of triple therapy and resection was 123 days (range, 55-372 days). Pathological complete response and major pathological response were observed in 16 and 24 patients, respectively. Median overall survival and progression-free survival were not reached. Treatment-related adverse events occurred in 74.2% of the patients (grade ≥3, 14.5%; grade ≥4, 4.8%). CONCLUSION: Combination of LEN, PD-1 and TACE showed a high rate of tumor response and convert resection in uHCC patients, with manageable toxicity.

Verapamil induces autophagy to improve liver regeneration in non-alcoholic fatty liver mice.

Verapamil can restore intracellular calcium homeostasis, increase the fusion of autophagosomes and lysosomes, reduce lipid droplet accumulation and inhibit inflammation and insulin resistance in high-fat-fed mice. The present study aimed to investigate verapamil's effect and its underlying liver regeneration mechanism in mice with non-alcoholic fatty liver. After 50% hepatectomy was performed, the changes of autophagy and liver regeneration were evaluated by detecting cell proliferation and autophagy at each time point. Then, 25mg/kg verapamil was injected intraperitoneally for 10 d before an operation in the mild to moderate fatty liver and severe fatty liver groups. The control group and mild to moderate fatty liver group reached the peak of proliferation at 24-48h after operation, and the mice with severe fatty liver and steatohepatitis reached the peak at 48-72h. Autophagy in the normal group and mild to moderate fatty liver group reached the peak 48 hours after operation. Verapamil injection can enhance autophagy, reduce the weight of fatty liver mice, improve liver function and liver regeneration. Verapamil can induce autophagy, improve hepatocyte function and promote hepatocyte regeneration through the mTOR independent signaling pathway, thus improving the process of liver regeneration after partial hepatectomy.

Long-Term Outcomes of Anatomic Versus Nonanatomic Resection in Hepatocellular Carcinoma Patients with Bile Duct Tumor Thrombus: A Propensity Score Matching Analysis.

BACKGROUND: Anatomic resection (AR) of the liver is generally recommended in hepatocellular carcinoma (HCC) patients. However, the benefits of AR and nonanatomic resection (NAR) in HCC patients with bile duct tumor thrombus (BDTT) are unknown. This study aimed to compare long-term outcomes of AR and NAR in HCC patients with BDTT after curative resection. PATIENTS AND METHODS: A total of 175 consecutive HCC patients with BDTT after curative resection between April 2009 and December 2017 were included. One-to-one propensity score matching (PSM) was performed to minimize the influence of potential confounders. Recurrence-free survival (RFS) and overall survival (OS) were compared between the cohorts. RESULTS: After PSM, 120 patients were analyzed. The AR group had better RFS than the NAR group (P = 0.010). Even though there was no statistically significant difference in OS (P = 0.140, power = 0.33), the 3- and 5-year OS rates in the AR group (52.4% and 44.2%, respectively) were obviously higher than those in the NAR group (35.4% and 30.4%, respectively). When patients were further stratified according to tumor size, better RFS and OS were observed in patients with small (≤ 5 cm) tumors after AR (P < 0.001 and P = 0.004, respectively). Multivariate analysis identified AR (P = 0.024) as an independent favorable prognostic factor for RFS in HCC patients with BDTT. CONCLUSIONS: AR is recommended for HCC patients with BDTT, especially in patients with small (≤ 5 cm) tumors.

Outcomes of laparoscopic bile duct exploration for choledocholithiasis with small common bile duct.

BACKGROUND: Laparoscopic cholecystectomy (LC) combined with laparoscopic common bile duct (CBD) exploration (LCBDE) is one of the main treatments for choledocholithiasis with CBD diameter of larger than 10 mm. However, for patients with small CBD (CBD diameter ≤ 8 mm), endoscopic sphincterotomy remains the preferred treatment at present, but it also has some drawbacks associated with a series of complications, such as pancreatitis, hemorrhage, cholangitis, and duodenal perforation. To date, few studies have been reported that support the feasibility and safety of LCBDE for choledocholithiasis with small CBD. AIM: To investigate the feasibility and safety of LCBDE for choledocholithiasis with small CBD. METHODS: A total of 257 patients without acute cholangitis who underwent LC + LCBDE for cholecystolithiasis from January 2013 to December 2018 in one institution were reviewed. The clinical data were retrospectively collected and analyzed. According to whether the diameter of CBD was larger than 8 mm, 257 patients were divided into large CBD group (n = 146) and small CBD group (n = 111). Propensity score matching (1:1) was performed to adjust for clinical differences. The demographics, intraoperative data, short-term outcomes, and long-term follow-up outcomes for the patients were recorded and compared. RESULTS: In total, 257 patients who underwent successful LC + LCBDE were enrolled in the study, 146 had large CBD and 111 had small CBD. The median follow-up period was 39 (14-86) mo. For small CBD patients, the median CBD diameter was 0.6 cm (0.2-2.0 cm), the mean operating time was 107.2 ± 28.3 min, and the postoperative bile leak rate, rate of residual CBD stones (CBDS), CBDS recurrence rate, and CBD stenosis rate were 5.41% (6/111), 3.60% (4/111), 1.80% (2/111), and 0% (0/111), respectively; the mean postoperative hospital stay was 7.4 ± 3.6 d. For large CBD patients, the median common bile duct diameter was 1.0 cm (0.3-3.0 cm), the mean operating time was 115.7 ± 32.0 min, and the postoperative bile leak rate, rate of residual CBDS, CBDS recurrence rate, and CBD stenosis rate were 5.41% (9/146), 1.37% (2/146), 6.85% (10/146), and 0% (0/146), respectively; the mean postoperative hospital stay was 7.7 ± 2.7 d. After propensity score matching, 184 patients remained, and all preoperative covariates except diameter of CBD stones were balanced. Postoperative bile leak occurred in 11 patients overall (5.98%), and no difference was found between the small CBD group (4.35%, 4/92) and the large CBD group (7.61%, 7/92). The incidence of CBDS recurrence did not differ significantly between the small CBD group (2.17%, 2/92) and the large CBD group (6.52%, 6/92). CONCLUSION: LC + LCBDE is safe and feasible for choledocholithiasis patients with small CBD and did not increase the postoperative bile leak rate compared with chole-docholithiasis patients with large CBD.

A nomogram based on combining systemic and hepatic inflammation markers for predicting microscopic bile duct tumour thrombus in hepatocellular carcinoma.

BACKGROUND: Bile duct invasion is a relatively rare event and is not well characterised in hepatocellular carcinoma (HCC). It remains very difficult to diagnose HCC with bile duct tumour thrombus (BDTT) before surgery. Increasing evidence has revealed that inflammation plays a critical role in tumorigenesis. This study aimed to develop nomograms based on systemic and hepatic inflammation markers to predict microscopic BDTT (micro-BDTT) before surgery in HCC. METHODS: A total of 723 HCC patients who underwent hepatectomy as initial therapy between January 2012 and June 2020 were included in the study. Logistic regression analysis was used to identify independent risk factors for micro-BDTT. The nomograms were constructed using significant predictors, including α-fetoprotein (AFP), alkaline phosphatase (ALP), direct bilirubin (DB), prognostic nutritional index (PNI), and γ-glutamyl transferase (γ-GT)/alanine aminotransferase (ALT). The prediction accuracies of the nomograms were evaluated using the area under the receiver operating characteristic (ROC) curve. RESULTS: AFP, ALP, DB, PNI, and γ-GT/ALT were independent risk factors for predicting micro-BDTT (P = 0.036, P = 0.004, P = 0.013, P = 0.012, and P = 0.006, respectively), which were assembled into the nomograms. The area under the ROC curve of the nomograms combining PNI and γ-GT/ALT for predicting micro-BDTT was 0.804 (95% confidence interval [CI]: 0.730-0.878). The sensitivity and specificity values when used in predicting micro-BDTT before surgery were 0.739 (95% CI: 0.612-0.866) and 0.781 (95% CI: 0.750-0.813), respectively. CONCLUSIONS: The nomogram based on combining systemic and hepatic inflammation markers is suitable for predicting micro-BDTT before surgery in HCC patients, leading to a rational therapeutic choice for HCC.

Total laparoscopic partial hepatectomy versus open partial hepatectomy for primary left-sided hepatolithiasis: A propensity, long-term follow-up analysis at a single center.

BACKGROUND: This trial was performed to compare short- and long-term outcomes after laparoscopic left-sided hepatectomy and open left-sided hepatectomy. Left-sided hepatectomy is a novel, minimally invasive operative technique for primary left-sided hepatolithiasis, but it has not been accepted widely due to the limited information about short- and long-term outcomes, effectiveness, and safety compared with the open approach. METHODS: Patients who underwent left-sided hepatectomy between January 2007 and December 2016 were reviewed and grouped into the open left-sided hepatectomy and left-sided hepatectomy groups, according to propensity score matching in terms of age, sex, body mass index, liver function, location of stone, hepatitis serology, and comorbidity on a ratio of 1:1. RESULTS: No significant differences were observed in the demographic characteristics of the 200 patients included in the study. For the left-sided hepatectomy group (100 patients) when compared to the open left-sided hepatectomy group (100 patients, the duration of hospital stay was less (10.3 vs 14.7 days, P< .001), the incidence of postoperative biliary fistulas (5% vs 14%, P = .003) and overall morbidity were less (25% vs 45%, P = .003), out of bed return to activity was expedited (2.0 vs 2.7 days, P< .001), and the rate of stone recurrence in the long-term follow-up was les (5.1% vs 17%, P = .003). CONCLUSION: Left-sided hepatectomy was associated with significantly lesser rate of stone recurrence, a shorter hospital stay, decreased morbidity and clinical biliary fistula rate, and expedited postoperative recovery compared with open left-sided hepatectomy.

Adenomas of the common bile duct in familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) or Gardner's syndrome is often accompanied by adenomas of the stomach and duodenum. We experienced a case of adenomas of the common bile duct in a 40-year-old woman with FAP presenting with acute cholangitis. Only 8 cases of adenomas or adenocarcinoma of the common bile duct have been reported in the literature in patients with FAP or Gardner's syndrome. Those patients presented with acute cholangitis or pancreatitis. Local excision or Whipple procedure may be the reasonable surgical option.

[Isolation of mouse primary hepatocytes by retrograde liver perfusion with catheterization via heart].

OBJECTIVE: To explore the effects of retrograde liver perfusion with catheterization via heart on the isolation of primary mouse hepatocytes. METHODS: In order to more efficiently isolate primary mouse hepatocytes, we improved the traditional two-step collagenase perfusion method. The liver perfusion catheter was inserted through right atrium and suprahepatic vena cava, and the perfusion velocity was controlled by the drip infusion with collagenase perfusate containing 10% of fetal calf serum. RESULTS: Total success rate of catheterization in the improved group was as high as 95%, and the success rate of first at ttempt in the improved group was significantly higher than that in the traditional group (94.7% vs. 68.8%). Liver perfusion in the improved group was symmetrical with the high yield of hepatocytes up to 1.07 x 10(6) per gram of mouse weight and 92.16% of average cell vitality, which were higher than those in the traditional group. CONCLUSION: The retrograde liver perfusion through the heart is a simple and easy-to-learn method to isolate mouse primary hepatocytes, which also could guarantee the satisfactory yield and vitality of primary hepatocytes.

Laparoscopic hepatectomy for liver metastases from colorectal cancer: a meta-analysis.

BACKGROUND: Liver resection can improve long-term survival for liver metastases from colorectal cancer. Laparoscopic hepatectomy is gaining increasing applications in colorectal liver metastases. We conducted a meta-analysis to investigate the safety, feasibility, and efficacy of laparoscopic liver resection compared with open hepatectomy for patients with colorectal liver metastases. MATERIALS AND METHODS: We performed both database and manual searching for comparative studies published before June 2013 without language or region restriction. Outcomes of interest consisted of perioperative outcomes and oncologic outcomes. RESULTS: Seven observational studies including 624 patients (241 in the laparoscopic group, 383 in the open group) were included. No randomized controlled trials were available. Pooled long-term oncologic outcomes of overall survival (hazard ratio=0.844; 95% confidence interval [CI] 0.412, 1.730; P=.644; I(2)=80.6%) and disease-free survival (hazard ratio=1.234; 95% CI 0.652, 2.333; P=.518; I(2)=79.6%) were similar in both groups. Subgroup analyses of studies with high quality and homogeneity confirmed the above outcomes. However, a lower incidence of R1 resection was observed in the laparoscopic group (relative risk [RR]=0.357; 95% CI 0.180, 0.708; P=.003; I(2)=0.0%) than in the open group. As for perioperative outcomes, laparoscopic hepatectomy presented a lower occurrence of postoperative complications (RR=0.647; 95% CI 0.477, 0.877; P=.005; I(2)=0.0%) and similar mortality (RR=0.625; 95% CI 0.12, 3.25; P=.576; I(2)=0.0%); less blood loss and less need for transfusion were also found in laparoscopic patients, whereas comparable operative time and length of hospital stay were required in the two groups. CONCLUSIONS: Laparoscopic hepatectomy is a safe procedure for colorectal liver metastases with long-term survival comparable to that of open hepatectomy. More prospective studies with adequate subgroup analyses are awaited to construct defined criteria for patient selection. Future randomized controlled trials are needed to eliminate potential selection bias and to confirm this conclusion.

Recurrence and survivals following hepatic resection for hepatocellular carcinoma with major portal/hepatic vein tumor thrombus.

AIM: To compare the recurrence and survivals between hepatocellular carcinoma (HCC) with major portal vein tumor thrombus (TT) and major hepatic vein TT after hepatic resection (HR). METHODS: A retrospective study was carried out with the medical records of 272 patients who underwent hepatic resection and thrombectomy for HCC with major portal vein (group A) or hepatic vein (group B) TT. The clinicopathological parameters, recurrence, survivals and prognostic significance associated with major portal or hepatic vein TT were analyzed. RESULTS: Patients in group A had a better median survival compared with their counterparts in group B (52 vs 38 weeks; P < 0.001). One-, 2- and 3-year survival rates were markedly greater in group A than in group B (50% vs 38.8%, 26% vs 15.9% and 11.4% vs 6.1%, respectively). There was no statistical difference in recurrence-free survival rate but extrahepatic recurrences were more often seen in group B. In multivariate analysis, TT location (hepatic veins vs portal veins), type of resection (anatomical vs non-anatomical) and liver cirrhosis (none/mild vs moderate/severe) were significant prognostic factors. CONCLUSION: Patients with HCC and major hepatic vein TT had higher incidence of extrahepatic metastases and worse overall survival after hepatic resection compared with patients with major portal vein TT. With preserved liver function, patients can receive aggressive treatments and survivals could be prolonged.

Expression of microRNA-150 targeting vascular endothelial growth factor-A is downregulated under hypoxia during liver regeneration.

Vascular endothelial growth factor (VEGF) is a factor that stimulates the proliferation of sinusoidal endothelial cells and hepatocytes during liver regeneration (LR). The present study aimed to screen and validate a microRNA (miRNA) that targets VEGF-A with relative specificity and to elucidate the potential association between hypoxia-inducible factor-1α (HIF­1α) and miRNA expression in the early phase of LR. Changes in the expression of miRNAs, which were predicted to target VEGF-A using online databases, were detected at 12, 24 and 48 h following a 70% partial hepatectomy (PHx) using quantitative PCR (qPCR). An inhibitor of the most downregulated miRNA was transfected into the primary hepatocytes in order to observe changes in the expression of the VEGF-A gene. The expression of HIF-1α protein in the regenerating liver was investigated using western blot analysis. The expression levels of HIF-1α mRNA (messenger RNA), the selected miRNA and VEGF-A mRNA in an anoxic model of hepatocytes was examined with qPCR. Of seven putative miRNAs, the expression of miR-150 exhibited the sharpest downregulation from 12-48 h. The micrOFF™ miR-150 inhibitor significantly elevated the expression levels of VEGF-A mRNA and protein 48 h after transfection. Thus, VEGF-A may be a downstream target of miR-150 during LR. Furthermore, HIF-1α protein expression increased to its highest level 24 h following PHx. miR-150 expression was inhibited and the expression of VEGF-A mRNA increased accordingly in the hypoxia-induced hepatocytes. Our results suggest that miR-150 expression is subject to negative regulation by HIF-1α.

A meta-analysis of perioperative outcomes of laparoscopic splenectomy for hematological disorders.

BACKGROUND: Due to changes in surgical trends, laparoscopic splenectomy (LS) has become the standard approach for most splenectomies performed for hematological disorders, barring any contraindications. The perioperative outcomes of LS for this indication have not been updated for several years. Controversy still surrounds whether LS should be performed for massive splenomegaly. The purpose of this meta-analysis was to evaluate the perioperative outcomes of laparoscopic splenectomy for hematological disorders. METHODS: Literature searches were conducted to identify studies comparing the perioperative outcomes of the laparoscopic and open approaches for hematological disorders. The results were pooled by using standard meta-analysis methods. RESULTS: Thirty-eight studies with a total of 2,914 patients comparing LS to open splenectomy (OS) for hematological disorders were identified. Mortality was low in both groups. The pooled complications of the LS group were significantly fewer than those of the OS group (-0.11, p < 0.001), and the NNT was 9 (95 % confidence interval, 6-20). For massive spleens, a similar result was observed (-0.12, p = 0.009). Accessory spleen resection and blood loss also were comparable between the two approaches. Additionally, LS was associated with longer operative times (57.38 min, p < 0.00001) and shorter hospital stays (2.48 days, p < 0.00001). CONCLUSIONS: LS is preferred compared to OS, based on lower complication rates and better handling of comorbid conditions. LS is associated with shorter hospital stays but longer operative times. We conclude that LS may be considered an acceptable option even in cases of a massive spleen. To strengthen the clinical evidence, more high-quality clinical trials on different issues are necessary.