Is conventional functional liver remnant volume higher than 40% still sufficient to prevent post-hepatectomy liver failure in jaundiced patients with hilar cholangiocarcinoma? A single-center experience in China.

OBJECTIVE: Our study aims to evaluate the predictive accuracy of functional liver remnant volume (FLRV) in post-hepatectomy liver failure (PHLF) among surgically-treated jaundiced patients with hilar cholangiocarcinoma (HCCA). METHODS: We retrospectively reviewed surgically-treated jaundiced patients with HCCA between June, 2000 and June, 2018. The correlation between FRLV and PHLF were analyzed. The optimal cut off value of FLRV in jaundiced HCCA patients was also identified and its impact was furtherly evaluated. RESULTS: A total of 224 jaundiced HCCA patients who received a standard curative resection (43 patients developed PHLF) were identified. Patients with PHLF shared more aggressive clinic-pathological features and were generally in a more advanced stage than those without PHLF. An obvious inconsistent distribution of FLRV in patients with PHLF and those without PHLF were detected. FLRV (continuous data) had a high predictive accuracy in PHLF. The newly-acquired cut off value (FLRV = 53.5%, sensitivity = 81.22%, specificity = 81.4%) showed a significantly higher predictive accuracy than conventional FLRV cut off value (AUC: 0.81 vs. 0.60, p < 0.05). Moreover, patients with FLRV lower than 53.5% also shared a significantly higher major morbidity rate as well as a worse prognosis, which were not detected for FLRV of 40%. CONCLUSION: For jaundiced patients with HCCA, a modified FLRV of 53.5% is recommended due to its great impact on PHLF, as well as its correlation with postoperative major morbidities as well as overall prognosis, which might help clinicians to stratify patients with different therapeutic regimes and outcomes. Future multi-center studies for training and validation are required for further validation.

The effectiveness of combined extra-hepatic bile duct resection in radically-resected cases with intrahepatic cholangiocarcinoma: a SEER-based retrospective cohort study and an external validation.

OBJECTIVE: To evaluate the effectiveness of the combined extra-hepatic bile duct resection (EHBDR) in cases with intrahepatic cholangiocarcinoma (IHCC) in terms of clinicopathological features and long-term survival. METHODS: Radically resected cases with IHCC from 2000 to 2020 were identified from Surveillance, Epidemiology, and End Results (SEER) database. Comparative analyses were performed between resected IHCC patients who received EHBDR and those without EHBDR. Moreover, an external validation was further performed based on a single-center cohort. RESULTS: A total of 1521 radically resected cases with IHCC (EHBDR: 189) were identified from SEER database. Comparable age, sex, race, marital status, liver cirrhosis, differentiation status, and adjuvant chemotherapy were acquired between two groups. EHBDR was associated with a higher incidence of adequate lymphadenectomy (P<0.001). The incidence of cases with T3-4 or N+ disease was significantly higher in EHBDR group (P<0.001). Adjuvant radiotherapy was more frequently performed in cases with EHBDR (P<0.001). EHBDR failed to brought any survival benefit and was associated with a worse prognosis even after matching. Similar findings have also been revealed in the external validation cohort (n=522, EHBDR: 117). EHBDR was associated with more extended resections, more aggressive tumor biological features, and worse prognosis. In the matched validation cohort, EHBDR was still associated with a higher incidence of early recurrence. CONCLUSION: EHBDR was an indicator of advanced stage and failed to brought any survival benefit. It is the tumor stage which really determines the prognosis. More in-depth analyses focusing on different situations of EHBDR with more detailed clinical data are required.

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.

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.

The prognostic value of combined preoperative PLR and CA19-9 in patients with resectable gallbladder cancer.

The platelet to lymphocyte ratio (PLR) is the marker of host inflammation and it is a potential significant prognostic indicator in various different tumors. The serum carbohydrate antigen 19-9 (CA19-9) is a tumor-associated antigen and it is associated with poor prognosis of gallbladder cancer (GBC). We aimed to analyze the prognostic value of the combination of preoperative PLR and CA19-9 in patients with GBC. A total of 287 GBC patients who underwent curative surgery in our institution was included. To analyze the relationship between PLR and CA19-9 and clinicopathological features. A receiver operating characteristic (ROC) curve was used to identify the optimal cutoff value for PLR and CA19-9. The Kaplan-Meier method was used to estimate the overall survival (OS). Meanwhile, the univariate and multivariate Cox regression models were used to assess the risk factors for OS. The cutoff values of 146.82 and 36.32U/ml defined as high PLR and high CA19-9, respectively. Furthermore, survival analysis showed that patients with PLR > 146.82 and CA19-9 > 36.32 U/ml had a worse prognosis than patients with PLR ≤ 146.82 and CA19-9 ≤ 36.32 U/ml, respectively. The multivariate analysis demonstrated that PLR (hazard ratio (HR) = 1.863, 95% CI: 1.366-2.542, P < 0.001) and CA19-9 (HR = 1.412, 95% CI: 1.021-1.952, P = 0.037) were independent prognostic factors in the GBC patients. When we combined these two parameters, the area under the ROC curve increased from 0.624 (PLR) and 0.661 (CA19-9) to 0.711. In addition, the 1-, 3-, and 5-year OS of group A (patients with PLR ≤ 146.82 and CA19-9 ≤ 36.32 U/ml), group B (patients with either of PLR > 146.82 or CA19-9 > 36.32 U/ml) and group C (patients with PLR > 146.82 and CA19-9 > 36.32 U/ml) were 83.6%, 58.6%, 22.5%, 52.4%, 19.5%, 11.5%, and 42.3%, 11.9%, 0%, respectively. The preoperative PLR and serum CA19-9 are associated with prognosis of patients with GBC. The combination of PLR and CA19-9 may serve as a significant prognostic biomarker for GBC patients superior to either PLR or CA19-9 alone.

Prognostic factors for resected cases with gallbladder carcinoma: A systematic review and meta-analysis.

OBJECTIVE: Current meta-analysis was performed to systematically evaluate the potential prognostic factors for overall survival (OS) among resected cases with gallbladder carcinoma (GBC). METHODS: PubMed, EMBASE, and the Cochrane Library were systematically retrieved and hazard ratio (HR) and its 95% confidence interval (CI) were directly extracted from the original study or roughly estimated via Tierney's method. Standard Parmar modifications were used to determine pooled HRs. RESULTS: A total of 36 studies with 11502 cases were identified. Pooled results of univariate analyses indicated that advanced age (HR=1.02, P =0.00020), concurrent gallstone disease (HR=1.22, P =0.00200), elevated preoperative CA199 level (HR=1.93, P <0.00001), advanced T stage (HR=3.09, P <0.00001), lymph node metastasis (HR=2.78, P <0.00001), peri-neural invasion (HR=2.20, P <0.00001), lymph-vascular invasion (HR=2.37, P <0.00001), vascular invasion (HR=2.28, P <0.00001), poorly differentiated tumor (HR=3.22, P <0.00001), hepatic side tumor (HR=1.85, P <0.00001), proximal tumor (neck/cystic duct) (HR=1.78, P <0.00001), combined bile duct resection (HR=1.45, P <0.00001), and positive surgical margin (HR=2.90, P <0.00001) were well-established prognostic factors. Pathological subtypes ( P =0.53000) and postoperative adjuvant chemotherapy ( P =0.70000) were not prognostic factors. Pooled results of multi-variate analyses indicated that age, gallstone disease, preoperative CA199, T stage, lymph node metastasis, peri-neural invasion, lymph-vascular invasion, tumor differentiation status, tumor location (peritoneal side vs hepatic side), surgical margin, combined bile duct resection, and postoperative adjuvant chemotherapy were independent prognostic factors. CONCLUSION: Various prognostic factors have been identified beyond the 8th AJCC staging system. By incorporating these factors into a prognostic model, a more individualized prognostication and treatment regime would be developed. Upcoming multinational studies are required for the further refine and validation.

Prognostic value of combined preoperative inflammatory marker neutrophil-lymphocyte ratio and platelet distribution width in patients with gallbladder carcinoma.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) and platelet distribution width (PDW) are associated with poor prognosis in various cancers. We aimed to analyze the prognostic value of the combination of preoperative NLR and PDW in patients with gallbladder carcinoma (GBC). METHODS: A total of 287 GBC patients who underwent curative-intent surgery in our institution was included. The relationship between NLR and PDW and clinicopathological features were analyzed. The receiver operating characteristic (ROC) curves were used to determine the optimal cutoff value for NLR and PDW. Overall survival (OS) was estimated using the Kaplan-Meier method. Meanwhile, the univariate and multivariate Cox regression models were used to assess the risk factors for OS. RESULTS: The optimal cutoff value of NLR and PDW was 3.00 and 14.76, respectively. In addition, survival analysis demonstrated that patients with NLR > 3.00 and PDW > 14.76 had a worse prognosis than patients with NLR ≤ 3.00 and PDW ≤ 14.76, respectively. The multivariate analysis showed that NLR and PDW were independent prognostic factors in the patients with GBC. When we combined NLR and PDW, the area under the ROC curve increased from 0.665 (NLR) and 0.632 (PDW) to 0.676. Moreover, the 1-, 3-, and 5-year OS of group A (patients with NLR ≤ 3.00 and PDW ≤ 14.76), group B (patients with either of NLR > 3.00 or PDW > 14.76) and group C (patients with NLR > 3.00 and PDW > 14.76) were 88.7%, 62.6%, 28.1%, 65.1%, 26.9%, 13.1%, and 34.8%, 8.3%, 0%, respectively. CONCLUSION: The combination of NLR and PDW may serve as a significant prognostic biomarker for GBC patients superior to either NLR or PDW alone.

Laparoscopic Left Hepatectomy for Intrahepatic Cholangiocarcinoma.

BACKGROUND: Minimally invasive surgery for intrahepatic cholangiocarcinoma (ICC) remains challenging, especially in advanced patients. PATIENT AND METHOD: A 66-year-old male was diagnosed with stage II ICC after a comprehensive evaluation and was scheduled for laparoscopic exploration and left hepatectomy. RESULTS: The pure laparoscopic left hepatectomy was completed in 240 min, employing a no-touch en bloc technique and lymphadenectomy skeletonization. The patient was discharged 6 days after the operation without any complications and received gemcitabine and cisplatin treatment postoperatively. There was no recurrence during 14 months of follow-up. CONCLUSIONS: Our experience demonstrates that when utilizing the no-touch en bloc technique, standardized lymphadenectomy through skeletonization, and effective control of bleeding, surgeons with extensive expertise in laparoscopic hepatectomy can achieve results comparable to open surgery.

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.

The significance of peri-neural invasion in patients with resected hilar cholangiocarcinoma: A single-center experience in China.

BACKGROUND: The significance of peri-neural invasion (PNI) in resected patients with hilar cholangiocarcinoma (HCCA) has been rarely explored. Our study was performed to evaluate the significance of PNI in resected HCCA patients in terms of tumor biological features and long-term survival. METHODS: We retrospectively reviewed surgically-treated HCCA patients between June, 2000 and June 2018. SPSS 25.0 software was used for statistical analysis. RESULTS: A total of 239 resected HCCA patients were included (No. PNI: 138). PNI indicated more aggressive tumor biological features. Major vascular reconstruction was more frequently performed in patients with PNI (34.8% vs 24.8%, P = 0.064). Patients with PNI shared a significantly higher percentage of surgical margin width <5 mm (29.0% vs 16.8%, P = 0.02). The proportion of patients with T1-2 disease (31.2% vs 40.6%, P = 0.085) or I-II disease (21% vs 34.7%, P = 0.014) was significantly lower in patients with PNI. The overall morbidity rate was significantly higher in patients with PNI (P = 0.042). A much worse overall survival (OS) (P = 0.0003) or disease-free survival (DFS) (P = 0.0011) in patients with PNI. Even after matching vital prognostic factors, a significantly worse OS (P = 0.0003) or DFS (P = 0.0002) was still observed in patients with PNI. PNI was an independent prognostic factor in both OS (P = 0.011) and DFS (P = 0.024). CONCLUSION: PNI indicated more aggressive tumor biological features and more advanced tumor stage in patients with resected HCCA. PNI can be an independent prognostic factor in both OS and DFS. Future multi-center studies covering various races or populations are required for further validation.

Meta-analysis of prognostic factors for overall survival and disease-free survival among resected patients with combined hepatocellular carcinoma and cholangiocarcinoma.

BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (CHCC-CC) is a rare subtype of primary liver malignancy and has been treated equally as intra-hepatic cholangiocarcinoma (IHCC) according to the 8th AJCC staging system. Owing to its rarity, its prognostic factors have been rarely explored and defined. METHODS: PubMed, EMBASE, the Cochrane Library and Web of Science were searched up till January 1st, 2023 and eligible studies were restricted to studies reported prognostic factors of resected CHCC-CC. Standard Parmar modifications were used to determine pooled univariable hazard ratios (HRs). RESULTS: A total of eleven studies with 1286 patients with resected classical CHCC-CC were finally included. Pooled results indicated that serum tumor biomarkers, including AFP, CA199, and CEA, were prognostic factors for postoperative overall survival (OS) and disease-free survival (DFS). Moreover, liver cirrhosis (P = 0.010), HBV infection (P = 0.030), and HCV infection (P < 0.001) were prognostic factors for OS. Age (HR = 1.03, P = 0.005) was a prognostic factor for DFS. Tumor size (OS: HR = 2, P < 0.001, DFS: HR = 2.15, P < 0.001), tumor number (OS: HR = 2.05, P < 0.001; DFS: HR = 1.96, P = 0.006), surgical margin (OS: HR = 2.33, <0.001001; DFS: HR = 2.35, P < 0.001), node metastasis (OS: HR = 2.96, P < 0.001; DFS: HR = 2.1, P < 0.001), vascular invasion (OS: HR = 2.17, P < 0.001; DFS: HR = 2.64, P < 0.001), and postoperative prophylactic trans-arterial chemotherapy embolization (PPTACE) (OS: HR = 1.67, P = 0.04; DFS: HR = 2.31, P < 0.001) were common prognostic factors for OS and DFS. CONCLUSION: Various risk factors unmentioned in the 8th AJCC staging system were identified. These promising findings would facilitate a more personalized predictive model and help clinicians to stratify patients with different survival outcomes.

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.

Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma: a systematic review of propensity score-matched studies.

Outcomes of laparoscopic liver resection (LLR) versus open LR (OLR) for intrahepatic cholangiocarcinoma (ICCA) are heterogeneous. We aimed to compare LLR and OLR for ICCA based on propensity-score-matched (PSM) studies. Two reviewers independently searched the online databases (PubMed, Embase, and Cochrane Library) for PSM studies that compared LLR and OLR for ICCA. The Ottawa-Newcastle Quality Assessment Scale with a cutoff of ≥ 7 was used to define higher-quality literature. Only 'high-quality' PSM analyses of the English language that met all our inclusion criteria were considered. A total of ten PSM trials were included in the analyses. Compared with OLR, although the lymph node dissection (LND) (RR = 0.67) and major hepatectomy rates were lower in the LLR group (RR = 0.87), higher R0 resections (RR = 1.05) and lower major complications (Clavien-Dindo grade ≥ III) (RR = 0.72) were also observed in the LLR group. In addition, patients in the LLR group showed less estimated blood loss (MD = - 185.52 ml) and shorter hospital stays as well (MD = - 2.75 days). Further analysis found the overall survival (OS) (HR = 0.91), disease-free survival (DFS) (HR = 0.95), and recurrence-free survival (HR = 0.80) for patients with ICCA after LLR were all comparable to those of OLR. LLR for selected ICCA patients may be technically safe and feasible, providing short-term benefits and achieving oncological efficacy without compromising the long-term survival of the patients.

Meta-analysis of Prognostic Factors for Overall Survival Among Resected Patients with Spontaneous Ruptured Hepatocellular Carcinoma.

OBJECTIVE: Our meta-analysis was performed to explore the prognostic factors for overall survival among post-hepatectomy patients with spontaneous ruptured hepatocellular carcinoma (SRHCC). METHODS: PubMed, EMBASE, the Cochrane Library, and Web of Science were all searched up for relevant studies regarding prognostic factors with SRHCC. RevMan5.3 software and Stata 14.0 software were used for statistical analysis. RESULTS: A total of nineteen studies with 1876 resected SRHCC patients were finally identified. Pooled results indicated that preoperative AFP (high vs low) (P = 0.003), concurrent liver cirrhosis (yes vs no) (P = 0.02), preoperative liver function (child A vs non-child A) (P = 0.0007), tumor size (large vs small) (P < 0.00001), tumor number (solitary vs multiple) (P = 0.002), satellite foci (yes vs no) (P = 0.0006), micro-vascular invasion (yes vs no) (P < 0.00001), type of hepatectomy (major or minor) (P = 0.04), surgical margin (R + vs R -) (P < 0.00001), and type of hepatectomy (emergency hepatectomy vs staged hepatectomy) (P = 0.005) were prognostic factors for overall survival among post-hepatectomy SRHCC patients. CONCLUSION: Apart from some conventional prognostic factors identified in resected patients with SRHCC, numerous prognostic factors have also been unmasked, which might provide clinical reference to stratify patients with different therapeutic regimes.

DNA damage repair mutations in pancreatic cancer- prognostic or predictive?

Objective: The efficacy of platinum-based chemotherapy (PtCh) for pancreatic cancer (PC) patients with DNA damage repair gene mutations (DDRm) compared to those without DDRm remains uncertain. Methods: After a thorough database searching in PubMed, Embase, and Web of Science, a total of 19 studies that met all the inclusion criteria were identified. The primary outcomes were overall survival (OS) and progression-free survival (PFS) for PC patients with DDRm versus those without DDRm after PtCh. Results: Patients with advanced-stage PC who have DDRm tend to have longer OS compared to patients without DDRm, regardless of their exposure to PtCh (HR=0.63; I2 = 66%). Further analyses indicated that the effectiveness of PtCh for OS was modified by DDRm (HR=0.48; I2 = 59%). After the first- line PtCh (1L-PtCh), the PFS of advanced-stage PC with DDRm was also significantly improved (HR=0.41; I2 = 0%). For patients with resected PC, regardless of their exposure to PtCh, the OS for patients with DDRm was comparable to those without DDRm (HR=0.82; I2 = 71%). Specifically, for patients with resected PC harboring DDRm who received PtCh (HR=0.85; I2 = 65%) and for those after non-PtCh (HR=0.87; I2 = 0%), the presence of DDRm did not show a significant association with longer OS. Conclusion: 1L-PtCh treatment is correlated with favorable survival for advanced-stage PC patients with DDRm. For resected-stage PC harboring DDRm, adjuvant PtCh had limited effectiveness. The prognostic value of DDRm needs to be further verified by prospective randomized controlled trials. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022302275.

Comparison of the clinical features and long-term prognosis of gallbladder neuroendocrine carcinoma versus gallbladder adenocarcinoma: A propensity score-matched analysis.

Gallbladder neuroendocrine carcinoma (GBNEC) is rare and characterized by a low degree of tumor differentiation. The clinical features of GBNEC versus gallbladder adenocarcinoma (GBADC) remain a subject of debate. A total of 201 GBADC and 36 GBNEC cases that underwent surgery resection between January 2010 and 2022 at the Department of Biliary Surgery, West China Hospital, Sichuan University were included. A 1:1 propensity score matching (PSM) was performed based on seven predefined variables: age, sex, the American Joint Committee on Cancer (AJCC) stage, resection status, perineural invasion (PNI), lymphovascular invasion (LVI), and degree of tumor differentiation. Compared with GBADC, GBNEC patients were younger (median age 56.0 vs 64.0 years; P = 0.001), and more patients presented with advanced stages of tumor (P = 0.003). Patients with GBNEC also had a higher rate of PNI (55.6% vs 22.4%; P < 0.001), and LVI (63.9% vs 45.80%; P = 0.658). Before PSM, GBNEC patients had inferior prognoses compared with GBADC patients with a shorter median overall survival (mOS) (15.02 vs 20.11 months; P = 0.0028) and a shorter median recurrence-free survival (mRFS) (10.30 vs 15.17 months; P = 0.0028). However, after PSM analyses, there were no differences in OS (mOS 18.6 vs 18.0 months; P=0.24) or RFS (mRFS 10.98 vs 12.02 months; P = 0.39) between the GBNEC and GBADC cases. After multivariate analysis, tumor diagnosis (GBNEC vs GBADC) was not identified as an independent risk factor for shorter RFS (P = 0.506) or OS (P = 0.731). Unfavorable pathological features, including advanced AJCC tumor stages, poor differentiation, presence of LVI, and positive resection margins (all P < 0.05), were independent risk factors for inferior OS and RFS. GBNEC is difficult to diagnose early and has a prognosis comparable to stage-matched poorly differentiated GBADC. Tumor diagnosis (either GBADC or GBNEC) was not an independent risk factor for the patient's OS. Unfavorable pathological features of the neoplasm are the main determinants.

The significance of countable and treatable metastatic liver disease in patients with gallbladder carcinoma after curative-intent surgery: A 10-year experience in China.

OBJECTIVE: Our study was performed to evaluate the significance of countable and treatable metastatic liver disease (CTMLD) in patients with gallbladder carcinoma (GBC) after curative-intent surgery. METHODS: Resected GBC patients between September 2010 and January 2021 were reviewed. Comparative analyses between patients with CTMLD and those without it were performed. A propensity score matching analysis was conducted for further validation. RESULTS: A total of 326 resected GBC patients were identified (33 with CTMLD). A significantly higher preoperative CA199 level was detected in those with CTMLD (p = 0.0160). Significantly higher incidences of major hepatectomy (p = 0.0010), lymph node metastasis (p < 0.0001), direct liver invasion (p < 0.0001), moderate to poor differentiation status (p < 0.0001), and T3-4 disease (p < 0.0001) were detected in patients with CTMLD. Even sharing comparable surgical margin status, patients with CTMLD still shared a significantly higher recurrence rate (93.9% vs. 57.3%, p < 0.0001) as well as a significantly higher recurrence rate within 6 months after surgery (63.6% vs. 14.7%, p < 0.0001). A significantly worse overall survival (median survival time: 12 vs. 33 months, p < 0.0001) or disease-free survival (median recurrence-free time: 6 vs. 30 months, p < 0.0001) was acquired in patients with CTMLD. After matching, a significantly higher early recurrence rate was still detected. Adjuvant chemotherapy seemed to have survival benefit for patients with CTMLD. CONCLUSION: CTMLD was an indicator of advanced disease and served as an independent predictor of early recurrence among resected GBC patients. Whether curative-intent surgery is superior to nonsurgical treatment among GBC patients with CTMLD remains to be explored in future prospective studies.

Neuroendocrine Component in Extrahepatic Cholangiocarcinoma is Associated with Better Survival: Data from the SEER Study.

INTRODUCTION: This study was performed to evaluate the prognostic value of the neuroendocrine component in patients with extrahepatic cholangiocarcinoma (EHCC). METHODS: Cases with EHCC derived from the SEER database were retrospectively reviewed and analyzed. The clinicopathological features and long-term survival were compared between patients with neuroendocrine carcinoma (NECA) and those with pure adenocarcinoma (AC). RESULTS: A total of 3277 patients with EHCC were included (62 patients with NECA and 3215 patients with AC). T stage (P = 0.531) and M stage (P = 0.269) were comparable between the two groups. However, lymph node metastasis was more frequently detected in NECA (P = 0.022). NECA was correlated with more advanced tumor stage than pure AC (P < 0.0001). Inconsistent differentiation status was also observed between the two groups (P = 0.001). The proportion of patients who received surgery was significantly higher in the NECA group (80.6% vs 62.0%, P = 0.003) while chemotherapy was more frequently performed among patients with pure AC (45.7% vs 25.8%, P = 0.002). Comparable incidence of radiotherapy was acquired (P = 0.117). Patients with NECA shared a better overall survival than those with pure AC (P = 0.0141), even after matching (P = 0.0366). The results of univariate and multivariate analyses indicated that the neuroendocrine component was a protective factor as well as an independent prognostic factor for overall survival (HR < 1, P < 0.05). CONCLUSION: Patients with EHCC with a neuroendocrine component shared a better prognosis than those with pure AC, and NECA could serve as a favorable prognostic factor for overall survival. Considering various unprovided but potentially confounding factors, future more well-conducted research is required.