Short- and long-term post-nephrectomy outcomes for retroperitoneal liposarcoma from a high-volume sarcoma center: a propensity score matching analysis.

BACKGROUND: Multivisceral en bloc resection with the ipsilateral kidney is commonly performed in patients with retroperitoneal liposarcoma (RLPS). We evaluated the effect of nephrectomy on short- and long-term outcomes in patients with RLPS. METHODS: Data from a prospectively maintained database of the Peking University Cancer Hospital Sarcoma Center between April 2011 and August 2022 were analyzed. We classified the RLPS patients who underwent surgery into nephrectomy group (NP) and non-nephrectomy group (non-NP). Patients were matched using a 1:1 propensity score to eliminate baseline differences between groups. Postoperative renal function outcomes, major morbidity, and mortality were analyzed to compare short-term outcomes after nephrectomy. Differences in local recurrence-free survival (LRFS) and overall survival (OS) were compared by Kaplan-Meier analysis with respect to oncological benefits. RESULTS: In the matched cohort, patients in the NP group had significantly higher postoperative eGFR and CKD stages, but none required dialysis. Patients between NP and non-NP had a comparable major morbidity (p = 0.820) and 60-day mortality (p = 0.475). Patients in the NP group had a higher 5-year LRFS rates than those in the non-NP group (34.5 vs. 17.8%, p = 0.015), and similar 5-year OS rates (52.4 vs. 47.1%, p = 0.401). Nephrectomy was an independent risk factor for LRFS, but not for major morbidity or OS. CONCLUSIONS: RLPS resection with nephrectomy is related to a mild progression of renal impairment; however, dialysis is rare. En bloc nephrectomy for complete resection of RLPS is safe and improves local control.

Toripalimab Plus Bevacizumab as First-line Treatment for Advanced Hepatocellular Carcinoma: A Prospective, Multicenter, Single-Arm, Phase II Trial.

PURPOSE: This phase II, multicenter, prospective, single-arm study aimed to evaluate the efficacy and safety of toripalimab plus bevacizumab in treating advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Treatment-naïve patients with advanced HCC received toripalimab 240 mg plus bevacizumab 15 mg/kg every 3 weeks. Primary endpoints included safety and tolerability, and objective response rate (ORR) assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RESULTS: Fifty-four patients were enrolled between Apr 17, 2020 and Dec 11, 2020. As assessed by the investigator according to RECIST v1.1, the ORR was 31.5% [95% confidence interval (CI), 19.5-45.6] and the lower bound of the 95% CI was above the pre-specified boundary of 10%. The independent review committee (IRC) assessed ORR according to modified RECIST (mRECIST) was 46.3% (95% CI, 32.6-60.4). The median progression-free survival were 8.5 months (95% CI, 5.5-11.0) and 9.8 months (95% CI, 5.6-not evaluable) assessed by the investigator according to RECIST v1.1 and IRC according to mRECIST criteria, respectively. The median overall survival (OS) was not reached, and the 12- and 24-month OS rates were 77.3% and 63.5%, respectively. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 27 patients (50.0%). The most common TEAEs were proteinuria (59.3%), hypertension (38.9%), aspartate aminotransferase increased (33.3%), amylase increased (29.6%), platelet count decreased (27.8%), and bilirubin increased (27.8%). CONCLUSIONS: Toripalimab plus bevacizumab showed a favorable efficacy and safety profile, supporting further studies of this combination regimen as a first-line treatment of advanced HCC.

[Corrigendum] Long non­coding RNA LINC00238 suppresses the malignant phenotype of liver cancer by sponging miR­522.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that two pairs of data panels featured in Figs. 2E and 6D, portraying the results from cell invasion and migration assay experiments, appeared to contain overlapping sections, such that data which were intended to show the results from differently performed experiments had apparently been derived from a smaller number of original sources. The authors were able to re­examine their original data (which was also presented to the Editorial Office), and realized that errors has been made in the compilation of Fig. 2. The proposed revised version of Fig. 2, now showing the results from the 'field 1' view of the data, is shown on the next page. Note that these errors did not significantly affect either the results or the conclusions reported in this paper,.All the authors agree to the publication of this Corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to correct this error; furthermore, they apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 25: 71, 2022; DOI: 10.3892/mmr.2022.12587].

Surgical outcomes of locally advanced gastrointestinal stromal tumors after multivisceral resection: A retrospective study of 64 patients at a single institution.

To analyze the outcome in patients who have undergone multivisceral resection (MVR) for locally advanced gastrointestinal stromal tumors (GISTs), and identify the risk factors for tumor recurrence and postoperative morbidity. Sixty-four patients who operated for locally advanced GISTs with MVR in PPeking University Cancer Hospital Sarcoma Center (PUCHSC) between 2013 and 2021 were identified. Clinicopathologic characteristics, surgical outcomes, recurrence, and 5-year recurrence-free and overall survival were evaluated. The mean age of the patients was 60 years. Mean tumor size was 11.1 cm. Complete resection was achieved in all patients. The estimated 5-year recurrence-free and overall survival were 86.6% and 90.0%, respectively. Independent factor of recurrence following surgery was mitotic count on multivariate analysis. Overall postoperative morbidity was 53.1% (n = 34). Severe morbidity was 21.9% (n = 14). The most common severe complication was clinically relevant pancreatic fistula (n = 12, 18.8%), followed by anastomotic leakage (n = 4, 6.3%) and Intraabdominal abscess (n = 4, 6.3%). Multivariate analysis showed that preoperative imatinib therapy could reduce overall morbidity. Long operation time, combined colectomy and pancreatectomy were independent risk factors for postoperative severe morbidity. Compared to partial pancreatectomy, pancreaticoduodenectomy (PD) was significantly increased the incidence of severe morbidity. In conclusion, compared to systemic therapy alone, the outcome of locally advanced GISTs after MVR was more favorable. Despite the high overall morbidity, the postoperative severe morbidity and mortality of MVR were acceptable. Preoperative imatinib therapy should be recommended whenever possible. Combined pancreatectomy and colectomy are associated with significant postoperative severe morbidities. PD should be thoroughly discussed and be subject to MDT approach before surgery.

Volume-based 18F-FDG PET/CT predicts prognosis and outcome of active surveillance for intra-abdominal desmoid tumor.

PURPOSE: Desmoid tumor (DT) is a rare monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Initial active surveillance is recommended by current guideline, and surgery is one of the main therapies for DT. Predicting the prognosis and outcome of active surveillance for intra-abdominal DT is pressing issue. METHODS: The study included eighteen patients with intra-abdominal DT. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) were measured. We analyzed their relationship with the outcome of active surveillance, as well as clinical, prognostic, and pathological data. RESULTS: The MTV and TLG of recurrent DT were significantly higher than those of non-recurrent DT (P < 0.001 and P = 0.00, respectively). The ROC curve suggested that the appropriate cutoff values for distinguishing recurrent DT from non-recurrent DT were 760.8 for MTV (sensitivity = 1, specificity = 0.857 and AUC = 0.929), and 1318.4 for TLG (sensitivity = 1, specificity = 0.786, and AUC = 0.911). The cutoff values of MTV and TLG significantly correlated with PFS using the Kaplan-Meier method (P = 0.002 and P = 0.007, respectively). MTV and TLG could distinguish DTs with subsequent progression from stable ones (P = 0.004 and P = 0.004, respectively). The ROC curve suggested that the appropriate cutoff values for distinguishing DTs with subsequent progression from stable ones were 197.1 for MTV (sensitivity = 0.9, specificity = 1, and AUC = 0.900), and 445.45 for TLG (sensitivity = 0.9, specificity = 1, and AUC = 0.900). CONCLUSION: Volume-based 18F-FDG-PET can predict prognosis of intra-abdominal DT. MTV and TLG can predict the outcome of active surveillance for intra-abdominal DT. MTV and TLG can potentially be predictors of surgical risk and difficulty.

Preoperative assessment of retroperitoneal Liposarcoma using volume-based 18F-FDG PET/CT: implications for surgical strategy and prognosis.

PURPOSE: Retroperitoneal liposarcoma (RLPS) poses a challenging scenario for surgeons due to its unpredictable biological behavior. Surgery remains the primary curative option for RLPS; however, the need for additional information to guide surgical strategies persists. Volume-based 18F-FDG PET/CT may solve this issue. METHODS: We analyzed data from 89 RLPS patients, measuring metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) and explored their associations with clinical, prognostic, and pathological factors. RESULTS: MTV, TLG of multifocal and recurrent RLPS were significantly higher than unifocal and primary ones (P < 0.001, P < 0.001, P = 0.003 and P = 0.002, respectively). SUVmax correlated with FNCLCC histological grade, mitotic count and Ki-67 index (P for G1/G2 = 0.005, P for G2/G3 = 0.017, and P for G1/G3 = 0.001, P < 0.001 and P = 0.024, respectively). MTG, TLG and SUVmax of WDLPS were significantly lower than DDLPS and PLPS (P for MTV were 0.009 and 0.022, P for TLG were 0.028 and 0.048, and P for SUVmax were 0.027 and < 0.001, respectively). Multivariable Cox analysis showed that MTV > 457.65 (P = 0.025), pathological subtype (P = 0.049) and FNCLCC histological grade (P = 0.033) were related to overall survival (OS). CONCLUSIONS: Our findings indicate that MTV is an independent prognostic factor for RLPS, while MTV, TLG, and SUVmax can preoperatively predict multifocal lesions, histological grade, and pathological subtype. Volume-based 18F-FDG PET/CT offers valuable information to aid in the decision-making process for RLPS surgical strategies.

Differential analysis of core-fucosylated glycoproteomics enabled by single-step truncation of N-glycans.

Alpha-1,6 fucosylation of N-glycans (core fucosylation, CF) represents a unique form of N-glycans and is widely involved in disease progression. In order to accurately identify CF glycoproteins, several approaches have been developed based on sequential cleavage with different glycosidases to truncate the N-glycans. Since multi-step sample treatments may introduce quantitation bias and affect the practicality of these approaches in large-scale applications. Here, we systematically evaluated the performance of the single-step treatment of intact glycopeptides by endoglycosidase F3 for CF glycoproteome. The single-step truncation (SST) strategy demonstrated higher quantitative stability and higher efficiency compared with previous approaches. The strategy was further practiced on both cell lines and serum samples. The dysregulation of CF glycopeptides between preoperative and postoperative serum from patients with pancreatic ductal adenocarcinoma was revealed, and the CF modifications of BCHE_N369, CDH5_N112 and SERPIND1_N49 were found to be potential prognostic markers. This study thus provides an efficient solution for large-scale quantitative analysis of the CF glycoproteome.

Identification of the γ-glutamyl cycle as a novel therapeutic target and 5-oxoproline as a new biomarker for diagnosing pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant solid tumours, and abnormal metabolic reprogramming in the tumour microenvironment is regarded as an important contributor to its pathogenesis. OBJECTIVES: As there is an urgency to identify new targets based on the metabolic features that are highly refractory to PDAC treatment, this study aimed to identify suitable therapeutic targets for PDAC. METHODS: In this study, gene set enrichment and Kyoto Encyclopedia of Genes and Genomes analyses were performed on 163 PDAC tissue samples and 165 normal pancreatic tissue samples from The Cancer Genome Atlas and Genotype-Tissue Expression databases to identify alterations in critical metabolites that may contribute to PDAC pathogenesis. Furthermore, ultra-performance liquid chromatography-tandem mass spectrometry was performed to identify significant metabolic pathways between 24 pairs of tumour and adjacent non-tumour tissues and between serum samples from PDAC patients and healthy donors. RESULTS: Fifty-one tissue metabolites and 26 serum metabolites were altered in PDAC. Among them, those in the γ-glutamyl cycle were the most substantially changed, and 5-oxoproline was the biomarker of PDAC with the most significantly decreased levels. CONCLUSIONS: The γ-glutamyl cycle and 5-oxoproline might be potential biomarkers and therapeutic targets to improve the diagnosis, therapy, and prognosis of PDAC.

Nimotuzumab Plus Gemcitabine for K-Ras Wild-Type Locally Advanced or Metastatic Pancreatic Cancer.

PURPOSE: In a phase IIb trial of nimotuzumab plus gemcitabine, substantial clinical benefits were observed in patients with locally advanced or metastatic pancreatic cancer (PC). Therefore, we conducted a phase III clinical study to verify the efficacy and safety of this combination regimen in patients with K-Ras wild-type tumors (ClinicalTrials.gov identifier: NCT02395016). PATIENTS AND METHODS: Eligible patients were randomly assigned to receive nimotuzumab (400 mg once per week) or placebo followed by gemcitabine (1,000 mg/m2 on days 1, 8, and 15, once every 4 weeks) until disease progression or unacceptable toxicity. The primary end point was overall survival (OS) and the secondary end points were progression-free survival (PFS), response rates, and safety. RESULTS: A total of 480 patients were screened; 92 patients were enrolled and 82 patients with K-Ras wild-type tumors were eligible. In the full analysis set, the median OS was 10.9 versus 8.5 months, while the restricted mean survival time (RMST) was 18.05 versus 11.14 months for the investigational versus control arm (ratio of control v investigation = 0.62 [0.40-0.97]; P = .036). Median PFS was 4.2 versus 3.6 months in the investigational versus control arm (log-rank P = .04; hazard ratio, 0.60 [0.37-0.99]) and the restricted mean PFS time was 8.08 versus 4.76 months (RMST ratio, 0.58 [0.38-0.90]; P = .036). Both OS and PFS were longer in the nimotuzumab group than in the placebo group. The objective response rates and disease control rates were 7% versus 10% and 68% versus 63% for the investigational and control groups, respectively. The incidence of adverse events were comparable between the two groups. CONCLUSION: In patients with locally advanced or metastatic K-Ras wild-type PC, nimotuzumab plus gemcitabine significantly improved OS and PFS with a good safety profile.

Cytoreductive surgery offers prognostic benefits in metastatic gastrointestinal stromal tumors with generalized progression following imatinib therapy: a single institute retrospective study.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Distant metastasis has been detected in approximately 50% of GIST patients at the first diagnosis. The surgical strategy for metastatic GIST with generalized progression (GP) after imatinib therapy remains unclear. METHODS: We recruited 15 patients with imatinib-resistant metastatic GIST. They received cytoreductive surgery (CRS) for tumor rupture, intestinal obstruction and gastrointestinal bleeding. We collected clinical, pathological and prognostic data for analyses. RESULTS: OS and PFS after R0/1 CRS were 56.88 ± 3.47 and 26.7 ± 4.12 months, respectively, when compared with 26 ± 5.35 and 5 ± 2.78 months after R2 CRS (P = 0.002 and P < 0.001, respectively). The OS of patients from the initiation of imatinib in the R0/1 group was 133.90 ± 15.40 months when compared with 59.80 ± 10.98 months in the R2 CRS group. There were two significant grade III complications after 15 operations (13.3%). No patient underwent reoperation. In addition, no perioperative death occurred. CONCLUSIONS: R0/1 CRS is highly probable to provide prognostic benefits for patients with metastatic GIST who experience GP following imatinib treatment. An aggressive surgical strategy for achieving R0/1 CRS can be deemed safe. If applicable, R0/1 CRS should be carefully considered in imatinib-treated patients with GP metastatic GIST.

Neoadjuvant therapy for sarcomatoid carcinoma of the pancreas: a case report and review of the literature.

BACKGROUND: Sarcomatoid carcinoma of the pancreas (SCP) is a rare type of malignant pancreatic neoplasm, and its prognosis is even worse than that of conventional pancreatic ductal adenocarcinoma (PDAC). Currently, there is no standard regimen for treating SCP, and the impact of systemic therapy on the survival of patients with SCP has not been well defined. CASE PRESENTATION: Herein, we report a 38-year-old Asian man diagnosed of local unresectable SCP with supraclavicular lymph node metastasis, radical excision after camrelizumab and anlotinib therapy, which resulted in a remarkable reduction in the size of primary tumor and complete remission of the metastatic lymph node. CONCLUSIONS: This is the first report of the use of immunotherapy and anti-angiogenesis therapy in a patient with SCP, which provides optimistic data to support the synergistic effect.

Efficacy and safety of anlotinib plus camrelizumab in treating retroperitoneal soft tissue sarcomas: a single-center retrospective cohort study.

Background: Conventional chemotherapy has limited therapeutic effects in retroperitoneal soft tissue sarcomas (RSTs), while anlotinib emerged as a novel multi-target tyrosine kinase inhibitor (TKI) for sarcomas. TKIs in combination with immunotherapy have demonstrated clinical activity in a variety of solid tumors. This study retrospectively analyzed the efficacy and safety of anlotinib plus camrelizumab for the treatment of RSTs. Methods: Patients with RSTs who received anlotinib plus camrelizumab at Peking University Cancer Hospital Sarcoma Center were enrolled. Response assessment was conducted every 3 cycles of treatment according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1). Treatment-related adverse events (TRAEs) were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Patients who had at least 1 response evaluation were analyzed. Results: In all, 57 RSTs cases including 35 males and 22 females were analyzed, with a median age of 55 years. The pathological subtypes included 38 cases of L-sarcoma (liposarcoma and leiomyosarcoma), and 19 cases of non-L-sarcoma. Two patients (3.5%) had complete response (CR) and 13 patients (22.8%) had partial response (PR), with an objective response rate (ORR) of 26.3%. There were 31 (54.4%) and 11 (19.3%) patients with stable and progressive disease, respectively, with a disease control rate of 80.7%. Patients with non-L-sarcoma had a significantly better response rate than those with L-sarcoma (ORR: 52.6% vs. 13.2%; P=0.0031). After a median follow-up of 15.8 months, the median progression-free survival (PFS) was 9.1 months, with 3- and 6-month PFS rates of 83.6% and 60.8%, respectively. Patients with non-L-sarcoma had a significantly longer median PFS than did those with L-sarcoma (median PFS: 11.1 vs. 6.3 months; P=0.0256). TRAEs occurred in 28 (49.1%) patients, and 13 (22.8%) patients had grade 3-4 TRAEs. Hypertension (24.6%), hypothyroidism (19.3%), and palmar-plantar erythrodysesthesia syndrome (12.3%) were the most common TRAEs. Conclusions: The combination of anlotinib and camrelizumab demonstrated possible therapeutic efficacy and safety in the treatment of RSTs, especially for non-L-sarcomas.

Delayed gastric emptying after aggressive surgery for retroperitoneal sarcoma - Incidence, characteristics, and risk factors.

Delayed gastric emptying (DGE) after aggressive resection of retroperitoneal sarcoma (RPS) has rarely been described. This study aimed to determine the incidence and characteristics of DGE after surgery for RPS and explore its potential risk factors. Patients with RPS who had undergone surgery between January 2010 and February 2021 were retrospectively analyzed. DGE was defined and graded according to the International Study Group of Pancreatic Surgery classification and classified as primary or secondary to other complications. Patients with clinically relevant DGE (crDGE, grade B+C) were compared to those with no or mild DGE (grade A). Multivariate logistic regression analysis of clinicopathological and surgical parameters was performed to identify risk factors for crDGE. Of the 239 patients studied, 69 (28.9%) had experienced DGE and 54 (22.6%) had experienced crDGE. Patients with primary and secondary DGE accounted approximately half and half. The most common concurrent complications included abdominal infection, postoperative pancreatic fistula, and abdominal bleeding. Patients with crDGE were more likely to have multifocal tumors and the liposarcoma subtype, with a larger tumor size, longer operating time, more resected organs, and a history of combined resection of the stomach, pancreas, small intestine, and/or colon. In multivariate analysis, the tumor size, operating time, and combined pancreatic resection were independent risk factors for crDGE. In conclusion, the current results indicated that approximately one-fourth of patients experienced DGE after aggressive surgery for RPS and that DGE was primary or secondary to other underlying conditions. A large tumor involving long, difficult surgery and combined pancreatic resection highly predicted the incidence of crDGE. The prevention and management of DGE remain challenging.

Activated Leukocyte Cell Adhesion Molecule (ALCAM), a Potential 'Seed' and 'Soil' Receptor in the Peritoneal Metastasis of Gastrointestinal Cancers.

Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) is a cell-cell adhesion protein conferring heterotypic and homotypic interactions between cells of the same type and different types. It is aberrantly expressed in various cancer types and has been shown to be a regulator of cancer metastasis. In the present study, we investigated potential roles of ALCAM in the peritoneal transcoelomic metastasis in gastrointestinal cancers, a metastatic type commonly occurred in gastro-intestinal and gynaecological malignancies and resulting in poor clinical outcomes. Specifically, we studied whether ALCAM acts as both a 'seed' receptor in these tumour cells and a 'soil' receptor in peritoneal mesothelial cells during cancer metastasis. Gastric cancer and pancreatic cancer tissues with or without peritoneal metastasis were compared for their levels of ALCAM expression. The impact of ALCAM expression in these tumours was also correlated to the patients' clinical outcomes, namely peritoneal metastasis-free survival. In addition, cancer cells of gastric and pancreatic origins were used to create cell models with decreased or increased levels of ALCAM expression by genetic knocking down or overexpression, respectively. Human peritoneal mesothelial cells were also genetically transfected to generate cell models with different profiles of ALCAM expression. These cell models were used in the tumour-mesothelial interaction assay to assess if and how the interaction was influenced by ALCAM. Both gastric and pancreatic tumour tissues from patients who developed peritoneal metastases had higher levels of ALCAM transcript than those without. Patients who had tumours with high levels of ALCAM had a much shorter peritoneal metastasis free survival compared with those who had low ALCAM expression (p = 0.006). ALCAM knockdown of the mesothelial cell line MET5A rendered the cells with reduced interaction with both gastric cancer cells and pancreatic cancer cells. Likewise, levels of ALCAM in both human gastric and pancreatic cancer cells were also a determining factor for their adhesiveness to mesothelial cells, a process that was likely to be triggered the phosphorylation of the SRC kinase. A soluble ALCAM (sALCAM) was found to be able to inhibit the adhesiveness between cancer cells and mesothelial cells, mechanistically behaving like a SRC kinase inhibitor. ALCAM is an indicator of peritoneal metastasis in both gastric and pancreatic cancer patients. It acts as not only a potential peritoneal 'soil' receptor of tumour seeding but also a 'soil' receptor in peritoneal mesothelial cells during cancer metastasis. These findings have an important therapeutic implication for treating peritoneal transcoelomic metastases.

Lusutrombopag for thrombocytopenia in Chinese patients with chronic liver disease undergoing invasive procedures.

PURPOSE: Probing efficacy and safety of lusutrombopag in Chinese chronic liver disease (CLD) and severe thrombocytopenia (PLT < 50 × 109/L) patients undergoing elective invasive procedures. METHODS: In this double-blind, parallel-group phase 3 study, 66 patients with CLD and severe thrombocytopenia were randomized 2:1 to lusutrombopag or placebo arm treatment regimens for seven days at 9 centers in China. Responders (PLT ≥ 50 × 109/L that increased to ≥ 20 × 109/L from the baseline and not received rescue therapy for bleeding) on Day 8 (the day after seven-day treatment) were assessed. PLT ≥ 50 × 109/L on or after Day 8 and within 2 days before invasive procedure (alternative criteria for not requiring platelet transfusion) were also analyzed. Adverse events (AEs) were recorded. RESULTS: The proportion of responders on Day 8 was evidently higher (p = 0.0011) in the lusutrombopag group (43.2%, 19/44) versus placebo (4.5%, 1/22). And 72.7% (32/44) patients receiving lusutrombopag met the alternative criteria for not requiring platelet transfusion, while 18.2% (4/22) in the placebo group. The median maximum PLT in lusutrombopag group increased to 80.5 × 109/L, and median time to reach maximum was 14.5 days. Compared with placebo, the lusutrombopag group had a lower incidence of bleeding events (6.8% versus 13.6%), and only one patient had thrombotic-related AE. Overall, the incidence of treatment-emergent AEs was comparable between two groups. CONCLUSIONS: Lusutrombopag was effective in raising PLT, diminishing platelet transfusion requirement, and documented a safety profile like the placebo in CLD and severe thrombocytopenia patients in a Chinese cohort undergoing elective invasive procedures. Chinese clinical trial registration number: CTR20192384.

Short- and long-term surgical outcomes of pancreatic resection for retroperitoneal sarcoma: A long-term single-center experience of 90 cases.

BACKGROUND AND OBJECTIVES: Resection of retroperitoneal sarcoma (RPS) en bloc with pancreas is challenging and controversial. This single-center retrospective study aimed to analyze the impact of pancreatic resection (PR) and its different types on short- and long-term outcomes in patients with RPS. METHODS: Data from 242 consecutive patients with RPS who underwent surgical treatment at the Peking University Cancer Hospital Sarcoma Center between January 2010 and February 2021 were analyzed. Out of these, 90 patients underwent PR, including pancreaticoduodenectomy (PD) in 31 and distal pancreatectomy (DP) in 59. RESULTS: Patients in the PR group had a higher major morbidity (37.8% vs. 14.5%) and mortality (8.9% vs. 1.3%) than those in the non-PR group, with a similar 5-year overall survival (OS) rate (46.9% vs. 53.6%). Patients in the PD and DP groups had a slight difference in major morbidity (48.4% vs. 32.2%), mortality (6.4% vs. 10.2%), and 5-year OS rates (43.3% vs. 49.3%). The PR type was not an independent risk factor for major morbidity or OS. CONCLUSIONS: PR in RPS resection was associated with increased morbidity and mortality with minimal influence on survival. Patients with RPS undergoing PD and DP showed slight differences in terms of safety and OS.

Pembrolizumab Versus Placebo as Second-Line Therapy in Patients From Asia With Advanced Hepatocellular Carcinoma: A Randomized, Double-Blind, Phase III Trial.

PURPOSE: We evaluated the efficacy and safety of pembrolizumab in patients from Asia with previously treated advanced hepatocellular carcinoma (HCC). METHODS: In a double-blind, phase III trial, 453 patients with advanced HCC and progression during or after treatment with or intolerance to sorafenib or oxaliplatin-based chemotherapy were randomly assigned in a 2:1 ratio to receive pembrolizumab (200 mg) or placebo once every 3 weeks for ≤ 35 cycles plus best supportive care. The primary end point was overall survival (one-sided significance threshold, P = .0193 [final analysis]). Secondary end points included progression-free survival (PFS) and objective response rate (ORR; one-sided significance threshold, P = .0134 and .0091, respectively [second interim analysis]; RECIST version 1.1, by blinded independent central review). RESULTS: Median overall survival was longer in the pembrolizumab group than in the placebo group (14.6 v 13.0 months; hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P = .0180). Median PFS was also longer in the pembrolizumab group than in the placebo group (2.6 v 2.3 months; hazard ratio for progression or death, 0.74; 95% CI, 0.60 to 0.92; P = .0032). ORR was greater in the pembrolizumab group (12.7% [95% CI, 9.1 to 17.0]) than in the placebo group (1.3% [95% CI, 0.2 to 4.6]; P < .0001). Treatment-related adverse events occurred in 66.9% of patients (grade 3, 12.0%; grade 4, 1.3%; grade 5, 1.0%) in the pembrolizumab group and 49.7% of patients (grade 3, 5.9%; grade 4, 0%; grade 5, 0%) in the placebo group. CONCLUSION: In patients from Asia with previously treated advanced HCC, pembrolizumab significantly prolonged overall survival and PFS, and ORR was greater versus placebo.

Expression and function of Siglec-15 in RLPS and its correlation with PD-L1: Bioinformatics Analysis and Clinicopathological Evidence.

Purpose: Retroperitoneal liposarcoma (RLPS) is a rare malignancy without effective treatment. Since current treatment for unresectable RLPS is unsatisfactory, immunotherapy and targeted therapy are urgently needed. Siglec-15 is a transmembrane protein highly homologous to PD-L1 and is involved in tumor immune escape. The biological function of Siglec-15 in RLPS, its prognostic relevance and its relationship with PD-L1 need to be further clarified. In this study, we aimed to explore the biological function of Siglec-15 in sarcomas through bioinformatics analysis, and we also evaluated Siglec-15 and PD-L1 expression in RLPS samples. The relationship between the expression of Siglec-15 and PD-L1 and their clinicopathological relevance and prognostic value were also investigated in clinical RLPS patients. Methods: The RNA sequencing data of 259 sarcoma cases and 48 RLPS cases from TCGA were used to analyze the Siglec-15 expression and the differentially expressed genes (DEG) related with Siglec-15 expression. In addition, DEGs were subsequently analyzed through the gene ontology (GO)/ Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network. Tumor specimens were obtained from 91 RLPS patients of our sarcoma center, and Siglec-15 and PD-L1 expression were evaluated using immunohistochemistry. The correlation between the expression level of these two markers as well as their correlation with clinicopathological factors and prognosis of RLPS patients was also assessed. Results: GEPIA analysis showed that the high expression of Siglec-15 was associated with poor sarcoma OS (P=0.034). A total of 682 differential genes were identified between the high and low expression groups of Siglec-15 in RLPS. Enrichment analysis of the KEGG pathway showed that Siglec-15 was related to the Hippo signaling pathway and the neuroactive ligand-receptor interaction. GO annotation analysis showed that the expression of Siglec-15 may thus be able to affect serine hydrolase activity, alongside signal receptor activator activity. The top 5 genes with the largest number of connection points are APOA1, F2, AHSG, AMBP, SERPINC1. In subsequent studies, we used 91 liposarcoma samples from our center for verification. Siglec-15 was expressed in 84.6% of RLPS cases, whereas PD-L1 was expressed in 17.6% of RLPS cases. A negative correlation was observed between Siglec-15 and PD-L1 expression (P=0.020). In this group of RLPS patients, high Siglec-15 expression was correlated with poorer disease-free survival (DFS) (P=0.021), and it was an independent predictor of DFS (hazard ratio: 2.298; 95% confidence interval: 1.154-4.576; P=0.018). However, we did not find a correlation between PD-L1 expression and overall survival or DFS in RLPS patients. Conclusion: The DEG and signaling pathways identified in the study could provide a preliminary understanding of the underlying molecular mechanisms of Siglec-15 in the development and progression of RLPS. High expression of Siglec-15 was a negative independent predictive factor for DFS of RLPS. The negative relationship between Siglec-15 and PD-L1 expression suggested that the Siglec-15 pathway might be an important supplement to PD-L1 treatment.