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Objective:To investigate the influence of lymphadenectomy on efficacy of patients with intrahepatic cholangiocarcinoma (ICC) at different locations.Methods:The retro-spective cohort study was conducted. The clinicopathological data of 123 patients with ICC who were admitted to the Affiliated Hospital of North Sichuan Medical College from January 2015 to January 2022 were collected. There were 78 males and 45 females, aged 55(rage, 50?60)years. All patients underwent radical resection. Observation indicators: (1) clinical characteristics of patients with ICC; (2) follow-up; (3) surgical situations in ICC patients with different number of lymph nodes dissected. Measurement data with normal distribution were represented as Mean± SD, and compari-son between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Kaplan-Meier method was used to draw survival curve and Log-Rank test was used for survival analysis. Results:(1) Clinical characteristics of patients with ICC. Of the 123 patients, 81 cases had peripheral ICC and 42 cases had central ICC. The albumin-bilirubin grade (grade 1, grade 2?3), preoperative lymph node metastasis risk assessment (low risk, high risk), the number of lymph nodes dissected (<6, ≥6), lymph node metastasis (positive, negative) were 57, 24, 51, 30, 49, 32, 15, 66 in patients with peripheral ICC, versus 19, 23, 17, 25, 14, 28, 16, 26 in patients with central ICC, showing significant differences in the above indicators between them ( χ2=7.40, 5.66, 8.17, 5.62, P<0.05). (2) Follow-up. All the 123 patients were followed up for 28(range, 21?38)months. The 3-year overall survival rate was 57.8% in the 81 patients with peripheral ICC, versus 32.3% in the 42 patients with central ICC, showing a significant difference between them ( χ2=5.98, P<0.05). Of the 42 patients with central ICC, there were 25 cases with high risk of lymph node metastasis before surgery and 17 cases with low risk of lymph node metastasis before surgery. Of the 25 central ICC patients with high risk of lymph node metastasis before surgery, the 3-year overall survival rate was 28.9% in the 18 cases with the number of lymph nodes dissected ≥6, versus 14.3% in the 7 cases with the number of lymph nodes dissected <6, showing a significant difference between them ( χ2=8.90, P<0.05). (3) Surgical situa-tions in patients with the different number of lymph nodes dissected. Of the 123 patients, cases with the number of lymph nodes dissected <6 and ≥6 were 63 and 60, and there was no significant difference in the operation time, intraoperative blood transfusion, postoperative complications, bile leakage, liver insufficiency, pulmonary infection, pleural effusion, abdominal effusion, or lymphatic leakage between them ( P>0.05). One patient might have multiple complications. Conclusions:The prognosis of patients with peripheral ICC is better than that of patients with central ICC. For patients with central ICC who are at high risk of lymph node metastasis before surgery, adequate lymph node dissection may result in a better prognosis.
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Pleckstrin homology (PH) domain leucine-rich repeat protein phosphatase 2 (PHLPP2) is a critical regulator of cellular homeostasis and acts as a tumor suppressor in multiple human cancers. However, its exact biological function in colorectal cancer (CRC) and the underlying molecular mechanism remain poorly understood. The correlation between the transcription and protein abundance of PHLPP2 was analyzed using proteomic and corresponding transcriptional data. Immunohistochemistry was used to validate the protein expression and the role of PHLPP2 in patient prognosis. In addition, a series of experiments in vitro and in vivo were performed to investigate the underlying molecular mechanism. Immunohistochemical staining of a CRC tissue microarray revealed that PHLPP2 protein expression was significantly downregulated compared to that in adjacent normal tissues. Low expression of PHLPP2 was an independent prognostic risk factor for poor survival. A nomogram established by integrating PHLPP2 expression and traditional clinicopathological factors achieved more reliable prognostic assessment in CRC patients. Additionally, PHLPP2 overexpression suppressed CRC cell migration, invasion and stemness in vitro as well as tumorigenesis in vivo. Further experiments revealed that upregulation of PHLPP2 increased ROS levels by suppressing the Nrf2-ARE signaling pathway, which inhibited the stemness of CRC cells. Moreover, incubation with sulforaphane, a selective chemical agonist of Nrf2, reversed this inhibitory effect in CRC. PHLPP2 acts as a tumor suppressor gene in CRC by restraining the Nrf2-ARE signaling pathway and increasing ROS levels, affecting the stemness of CRC cells. These anticancer molecular mechanisms indicate PHLLPP2's significant clinical value in prognosis prediction and targeted therapy.
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BACKGROUND: Curative resection of hilar cholangiocarcinoma (HC) is typically carried out using open surgery. In the present study, we examined the safety (postoperative complication) and effectiveness (resection margin status and patient survival) of minimally invasive surgery (MIS) for HC. METHODS: This retrospective analysis included 158 patients receiving MIS for HC at 10 participating centers between December 2013 and November 2019. Patient demographics, surgical outcomes, and oncological outcomes were retrospectively analyzed. RESULTS: Clinical information obtained from 10 different clinical centers did not show any evident cohort-bias clustering. One hundred and twenty-six (79.7%) patients underwent LRHC, 12 (7.6%) patients underwent RARHC, conversion to an open procedure occurred in 20 (12.7%) patients. The operation time and estimated blood loss were 410.8 ± 128.9 min and 477.8 ± 706.3 mL, respectively. The surgical radicality of the 158 patients was R0, 129 (81.6%); R1, 20 (18.4%) and R2, 9 (5.7%). Grades I-II complications was occurred in 68 (43.0%) patients. Severe morbidity (grade III-V) occurred in 14 (8.7%) patients. The median overall survival in whole cohort was 25.4 months. The overall survival rate was 67.6% at year 1, 28.8% at year 3, and 19.2% at year 5. Comparing the first half of MISHC performed by each center with the following cases, the operation time and postoperative hospital stay does not decrease with the increasing cases. On literature review, MISHC is non-inferior to open surgery at least in perioperative period. CONCLUSIONS: In this Chinese MIS for HC multicenter study, the largest to date, long-term overall survival rates after MIS appear comparable to those reported in current open series. Further randomized controlled trials are necessary to assess the global impact of MISHC.
