Unraveling early recurrence of risk factors in Gallbladder cancer: A systematic review and meta-analysis.

BACKGROUND: Gallbladder cancer (GBC) is the most prevalent biliary tract tumor characterized by a high incidence of recurrence, even after curative-intent surgery. The object of this systematic review and meta-analysis was to investigate the risk factors related to early recurrence (ER). METHODS: A systematic literature review was conducted in PubMed, Embase, Cochrane Library, and Web of Science to identify published articles up to February 2024. Data on risk factors associated with ER reported by two or more studies were collected. Selection of different effect models based on data heterogeneity. RESULTS: Out of 6497 initially identified articles based on our search strategies, only 5 were eligible and included in this meta-analysis and 12 ER-related factors were collected. The overall recurrence rate was reported between 32.3% and 61.0 %, and the ER rate ranged from 19.6% to 26.5 %. Concentrations of CA19-9 (OR 3.03 95 % CI 2.20-4.17) and CEA (OR 1.85 95 % CI 1.24-2.77), tumor differentiation (OR 2.79, 95 % CI 1.86-4.20), AJCC T stage (OR 7.64, 95%CI 3.40-17.18), lymphovascular invasion (OR 2.71, 95 % CI 1.83-4.03), perineural invasion (OR 2.71, 95 % CI 1.79-4.12), liver involvement (OR 5.69, 95%CI 3.78-8.56) and adjuvant therapy (OR 2.19, 95 % CI 1.06-4.55) were identified as the risk factors of ER. CONCLUSION: This study may provide valuable insights for early identification of increased ER risk and making informed decisions regarding the comprehensive diagnosis and treatment of patients with GBC. To draw more definitive conclusions, there is a need for high-quality prospective studies involving multiple centers and diverse racial populations.

Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood. METHODS: To address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue. RESULTS: Through the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs. CONCLUSIONS: This study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression.

Comparison of the upfront surgery and neoadjuvant therapy in resectable and borderline resectable pancreatic cancer: an updated systematic review and meta-analysis.

Pancreatic cancer is a malignant disease with a dismal prognosis. While neoadjuvant therapy has shown promise in the treatment of pancreatic cancer, its role remains a subject of controversy among physicians. We aimed to evaluate the benefits of neoadjuvant therapy in patients with resectable and borderline resectable pancreatic cancer. Eligible studies were identified from MEDLINE, Embase, Cochrane Library, and Web of Science. Studies comparing neoadjuvant therapy with upfront surgery (with or without adjuvant therapy) in resectable and borderline resectable pancreatic cancer were included. The primary endpoint assessed was overall survival. A total of 10,022 studies were identified, and the meta-analysis finally enrolled 50 revealed studies. The meta-analysis suggested that neoadjuvant therapy significantly improved the overall survival (HR 0.74, p < 0.001) and recurrence-free survival (HR 0.75, p = 0.006) compared to the upfront surgery approach. Furthermore, neoadjuvant therapy leads to favorable postoperative outcomes, with an enhanced R0 resection rate (OR 1.90, p < 0.001) and reduced lymph node metastasis (OR 0.36, p < 0.001) and perineural invasion (OR 0.42, p < 0.001), although it is associated with a reduced resection rate (OR 0.42, p < 0.001). In addition, patients treated with neoadjuvant therapy experience superior survival benefits compared to those undergoing adjuvant therapy (HR 0.87, p = 0.019). These results are further corroborated by the subgroup analysis of randomized controlled trials. Neoadjuvant therapy has the potential to provide survival benefits and improve postoperative long-term outcomes for patients with resectable and borderline resectable pancreatic cancer. However, to validate and reinforce these findings, further well-designed and large trials are required.

Prognostic Significance of Tumor Necrosis in Patients with Gallbladder Carcinoma Undergoing Curative-Intent Resection.

BACKGROUND: Tumor necrosis has been indicated to correlate with dismal survival outcomes of a variety of solid tumors. However, the significance and prognostic value of tumor necrosis remain unclear in gallbladder carcinoma. The aim of this research is to explore the relationships between necrosis with long-term survival and tumor-related biological characteristics of patients with gallbladder carcinoma. PATIENTS AND METHODS: Patients with gallbladder carcinoma who accepted curative-intent resection in West China Hospital of Sichuan University (China) between January 2010 and December 2021 were retrospectively analyzed. Tumor necrosis was determined by staining the patient's original tissue sections with hematoxylin and eosin. Based on the presence of tumor necrosis, the pathologic features and survival outcomes were compared. RESULTS: This study enrolled 213 patients with gallbladder carcinoma who underwent curative-intent surgery, of whom 89 had tumor necrosis. Comparative analyses indicated that patients with tumor necrosis had more aggressive clinicopathological features, such as larger tumor size (p = 0.002), poorer tumor differentiation (p = 0.029), more frequent vascular invasion (p < 0.001), presence of lymph node metastasis (p = 0.014), and higher tumor status (p = 0.01), and experienced poorer survival. Univariate and multivariate analyses revealed that tumor necrosis was an independent prognostic factor for overall survival (multivariate: HR 1.651, p = 0.026) and disease-free survival (multivariate: HR 1.589, p = 0.040). CONCLUSIONS: Tumor necrosis can be considered as an independent predictive factor for overall survival and disease-free survival among individuals with gallbladder carcinoma, which was a valuable pathologic parameter.

Comparison of clinicopathological characteristics and long-term survival between patients with gallbladder adenosquamous carcinoma and pure gallbladder adenocarcinoma after curative-intent surgery: a single-center experience in China and a meta-analysis.

Objective: The aim of the study was to evaluate the similarities and differences between gallbladder adenosquamous carcinoma (GBASC) and pure gallbladder adenocarcinoma (GBAC). Methods: Patients with GBASC and GBAC from 2010 to 2020 were analyzed in terms of clinicopathological features and long-term survival. Moreover, a meta-analysis was also performed for further validation. Results: Our experience: A total of 304 patients with resected GBC were identified, including 34 patients with GBASC and 270 patients with GBAC. Patients with GBASC had a significantly higher preoperative CA199 level (P <0.0001), a significantly higher incidence of liver invasion (P <0.0001), a relatively larger tumor size (P = 0.060), and a significantly higher proportion of patients with T3-4 (P <0.0001) or III-IV disease (P = 0.003). A comparable R0 rate was obtained between two groups (P = 0.328). A significantly worse overall survival (OS) (P = 0.0002) or disease-free survival (DFS) (P = 0.0002) was observed in the GBASC. After propensity score matching, comparable OS (P = 0.9093) and DFS (P = 0.1494) were obtained. Clear margin (P = 0.001), node metastasis (P <0.0001), T stage (P <0.0001), and postoperative adjuvant chemoradiotherapy (P <0.0001) were independent prognostic factors for OS for the entire cohort. Adjuvant chemoradiotherapy had a survival benefit for patients with GBAC, while the survival benefit was still being validated in patients with GBASC. Meta-analysis: With our cohort incorporated, a total of seven studies involving 1,434 patients with GBASC/squamous carcinoma (SC) were identified. GBASC/SC shared a worse prognosis (P <0.00001) and more aggressive tumor biological features than GBAC. Conclusion: GBASC/SC shared more aggressive tumor biological features and a much worse prognosis than those with pure GBAC.

The influence of resection margin width in patients with intrahepatic cholangiocarcinoma: a meta-analysis.

BACKGROUND: Some studies have pointed out that a wide resection margin can improve the prognosis of intrahepatic cholangiocarcinoma, but some researchers disagree and believe that a wide margin may increase complications. The optimal margin length of intrahepatic cholangiocarcinoma is controversial. METHOD: The literature was searched in PubMed, MedLine, Embase, the Cochrane Library, and Web of Science until December 31, 2021, to evaluate the postoperative outcomes of patients with different margin width after resection. Odds ratios (ORs) with 95% confidence intervals were used to determine the effect size. RESULT: A total of 11 articles were included in this meta-analysis, including 3007 patients. The narrow group had significantly lower 1-, 3-, and 5-year overall survival rates and recurrence-free survival rates than the wide group. Postoperative morbidity and prognostic factors were also evaluated. CONCLUSION: A resection margin width of over 10 mm is recommended in intrahepatic cholangiocarcinoma patients, especially in patients with negative lymph node and early tumor stage. When the resection margin width cannot be greater than 10 mm, we should ensure that the resection margin width is greater than 5 mm.

Comparison of clinicopathological characteristics of mucinous adenocarcinoma and conventional adenocarcinoma of gallbladder.

BACKGROUND: Gallbladder mucinous adenocarcinoma (GBMAC) is a rare type of gallbladder malignant tumor, whereas little is known regarding the clinicopathological features and surgical outcomes of GBMAC. METHODS: From January 2000 till December 2015, 54 GBMAC patients who underwent curative-intent surgical resection at our institution were retrospectively reviewed. We compared the clinicopathological features and surgical outcomes of these GBMAC patients with a relatively large cohort of surgically resected conventional gallbladder adenocarcinoma (GBAC) patients without existence of mucinous components. RESULTS: The clinicopathological features of GBMAC were significantly different from conventional GBAC, including poorer tumor differentiation (P < 0.001), higher CA19-9 levels (P < 0.001), larger tumor sizes (P = 0.020), advanced AJCC tumor stage (P = 0.002), higher frequency of liver parenchyma invasion (P = 0.020), portal vein invasion (P = 0.003), lymph node metastasis (P = 0.016), lympho-vascular invasion (P < 0.001) and perineural invasion (P = 0.025). Relative to conventional GBAC patients, GBMAC patients showed significantly worse overall survival (OS) (29.0 vs 15.0 months; P < 0.001). Multivariate analysis confirmed the surgical margin (P = 0.046), tumor differentiation grade (P = 0.018), lymph node metastasis (P = 0.024), and presence of signet-ring cell component (P = 0.005) as independent prognostic factors influencing OS of patients with GBMAC. CONCLUSION: GBMAC always had more aggressive biological behaviors and poor survival outcomes even after curative surgery. GBMAC patients with the presence of signet-ring cell component showed even worse survival outcome.

Clinicopathological characteristics and outcome of primary sarcomatoid carcinoma of the gallbladder.

Purpose: Our study aims to examine the clinicopathological features, disease progression, management, and outcomes of gallbladder sarcomatoid carcinoma (GBSC) patients. Methods: Between January 2000 and December 2020, 50 gallbladder cancer (GBC) patients who received surgical treatment and were pathologically verified as GBSC at our institution were enrolled. The clinical and pathological features and survival of these patients were retrospectively reviewed. Results: The median overall survival (OS) of GBSC patients was 14.5 months, and the 1-, 2- and 3-year OS rates were 68.0%, 32.0%, and 10.0%, respectively. The median progression-free survival (PFS) was 10.0 months, and the 1-, 2-, and 3-year PFS rates were 42.0%, 16.0%, and 2.0%, respectively. Patients who received radical resection had obviously better OS (18.0 vs. 7.0 months, P<0.001) and PFS (12.0 vs. 5.0 months, P<0.001) than those who underwent palliative resection. Multivariate analysis revealed that vascular invasion (P=0.033), curative operation (P<0.001) and postoperative chemotherapy (P=0.033) were independent risk factors for PFS. We further identified postoperative chemotherapy (P=0.010) and curative operation (P<0.001) as independent prognostic factors affecting the OS of GBSC patients. After curative surgery, patients who underwent S-1-based chemotherapy showed significantly longer recurrence-free survival (RFS) than those who underwent other chemotherapy regimens (20.0 vs 11.0 months, P=0.028). Conclusion: GBSC patients always have aggressive biological behaviors and remarkably poor prognoses. Most GBSC patients are diagnosed in advanced stages, and timely radical operation together with postoperative chemotherapy is important. S-1-based chemotherapy may be a selectively efficient regimen to prolong the survival of GBSC patients.

Research of a Safe and Simplified Intertransverse Process Approach for the Lower Thoracic Interbody Surgery.

OBJECTIVE: To assess a safe surgical approach for intertransverse process lower thoracic intervertebral body fusion (ITIF) based on measurements from enhanced three-dimensional CT reconstruction, cadaver simulated operation, and patient operation. METHODS: Enhanced three-dimensional CT image reconstruction was performed for 20 healthy volunteers on thoracic segments T8-T12. The length of the transverse process (LTP), distance between the upper and lower transverse processes (DULTP), remote distance of the transverse process (RDTP), height of the extraforaminal intervertebral space (HEIS), and oblique diameter of the intervertebral space (ODIS) were measured and recorded. The blood vessels of the intertransverse lower thoracic region were observed, and their internal diameters were measured. The rib-intervertebral space relationship for T10/11 and T11/12 was measured in 104 patients of the thoracic skeleton. Then, based on the data from the CT measurements, simulated surgery was performed on six human cadavers at the T11/12 level. An ankylosing spondylitis (AS) patient with a fracture of the T10/11 level was eventually operated on with the ITIF technique. RESULTS: No significant difference was found between the lengths of the left and right thoracic transverse processes. The relationship of the values of the LTP and RDTP for the measured vertebrae were found to be as follows:T8 > T9 > T10 > T11 > T12. For HEIS and DULTP, T8-9 < T9-10 < T10-11 < T11-12. The results for the ODIS were as follows: T8-T9 < T9-T10 < T10-T11 < T11-T12. The blood vessel inner diameter of T11-12 was less than that of T10-11, while there was no significant difference between the diameters for T8-9 and T11-12. Almost half of the volunteer's T10/11 intervertebral spaces were covered posteriorly by the 11th rib (45.19% on left and 41.35% on right), while for most patients, the T11/12 intervertebral space was not covered by the 12th rib (98.08%). According to the cadaver experiments, intervertebral bone grafting and ipsilateral pedicle screw fixation were performed to simulate the operation. One patient with a combined AS and T10/11 fracture was then operated on with the ITIF technique and followed up for 3 years with satisfactory results. CONCLUSION: As verified by 3D CT reconstruction measurements, cadaver simulation surgery and patient operation with follow-up, the intertransverse process approach for some T10/T11 and almost all T11/T12 segments is a safe surgical pathway for operations such as ITIF, fracture bone grafting, clearance of focal lesions.

Elevated Platelet Distribution Width Predicts Poor Prognosis in Gallbladder Carcinoma.

BACKGROUND: Previous studies have demonstrated that platelet distribution width (PDW) is a reliable predictor of prognosis of a variety of tumors. Nevertheless, the prognostic value of PDW in gallbladder carcinoma (GBC) remains unknown. We aimed to explore the correlation between PDW and prognosis in patients with GBC. METHODS: A total of 303 patients with GBC who underwent curative surgery between January 2005 and February 2017 were enrolled. The relationship between PDW and clinicopathological features was analyzed. Receiver operating characteristic (ROC) curve was used to identify the optimal cutoff value of PDW. The overall survival (OS) rate was estimated by Kaplan-Meier method. Meanwhile, univariable and multivariable Cox regression model were used to evaluate the risk factors for OS. RESULTS: There was significant correlation between elevated PDW and AJCC stage. In addition, survival analysis revealed that the patients with PDW>14.95 have a worse prognosis than patients with PDW14.95 (P < 0.001). The multivariable Cox regression model analysis demonstrated that PDW was an independent prognostic factor in GBC patients (hazard ratio=1.976, 95% confidence interval:1.474-2.650, P<0.001). CONCLUSION: Elevated PDW can predict poor prognosis in GBC patients, and further studies are needed to verify the reliability and clarify the exact molecular mechanistic of PDW in GBC.