Postoperative Disease-free Survival Research Articles

Preoperative Clinical and Ultrasonographic Predictors for Aggressive Behaviors in Sporadic Medullary Thyroid Carcinomas.

Objective: To explore the clinical and ultrasonographic predictors for aggressive behaviors preoperatively in sporadic medullary thyroid carcinomas (MTCs). Materials and Methods: The preoperative clinical and ultrasonographic characteristics of patients diagnosed with MTCs between January 2009 and May 2022 were retrospectively reviewed. MTCs were described and categorized according to the American College of Radiology (ACR) thyroid imaging reporting and data system classification by 2 radiologists. Interobserver agreement was evaluated by kappa test. Univariate and multivariate analyses were performed to identify predictors of aggressive behaviors in MTCs. The log-rank test was utilized to compare differences in Kaplan-Meier (K-M) curves for postoperative disease-free survival (PDFS). Results: A total of 120 patients were enrolled in the final study. Male sex was significant risk factor for metastasis, perithyroidal invasion, and lateral cervical lymph node (LCLN) metastasis [odds ratio (OR): 3.109, P = .019; OR: 5.316, P = .018; OR: 5.154 P = .012, respectively]. The kappa values for all ultrasonic characteristics were high (ranged from 0.811 to 0.941). Size, focality, and margin of the nodule were independent risk factors for metastasis, as well as for LCLN metastasis. Whereas margin (P < .001) and a subcapsular location (P = .021) were risk factors for perithyroidal invasion. According to K-M analysis, PDFS of patients differed significantly between groups with/without metastasis (P < .001), groups with/without perithyroidal extension (P < .001) and groups with/without LCLN metastasis (P < .001). Conclusions: Male sex is an independent risk factor for metastasis, perithyroidal invasion, and LCLN metastasis. The large size (≥2.55 cm for metastasis, ≥2.15 cm for LCLN metastasis, respectively), multifocality, and irregular margin of nodules were independent risk factors for both metastasis and LCLN metastasis. Extrathyroidal extension and a subcapsular location were risk factors for perithyroidal invasion. Moreover, patients with metastasis/perithyroidal extension/LCLN metastasis exhibited worse PDFS.

Cholinesterase as a predictor of skeletal muscle loss after gastrectomy for gastric cancer.

Cholinesterase is a classical nutritional and inflammatory marker. The aim of the present study was to evaluate the value of cholinesterase as a predictive marker for postoperative skeletal muscle loss after gastrectomy for gastric cancer. The study comprised 68 patients who had undergone gastrectomy for gastric cancer. Skeletal muscle mass was evaluated using skeletal mass index, and major skeletal muscle loss was defined as less than or equal to the median change rate (1-year postoperative/preoperative) of skeletal mass index in all patients. We explored the relationship between postoperative major skeletal muscle loss and disease-free survival and overall survival. Then we investigated the relationship between change rate of skeletal muscle index and serum cholinesterase levels after gastrectomy. The median value of change rate of skeletal mass index was 0.93. Postoperative major skeletal muscle loss was significantly associated with disease-free survival after gastrectomy (P=0.003). Although major skeletal muscle loss had worse overall survival, it was not significant (P=0.058). The change rate of skeletal mass index and cholinesterase had a stronger positive correlation compared with other nutritional indices according to Spearman's rank correlation coefficient (r=0.438, P≤0.001). Evaluation of serum cholinesterase levels may be valuable for predicting postoperative skeletal muscle loss after gastrectomy, suggesting the importance of cholinesterase in postoperative nutritional management of patients with gastric cancer.

Abstract PO2-08-06: Metformin may improve the outcome of patients with breast cancer and type 2 diabetes mellitus through the effect of tumor immune microenvironment

Abstract Metformin, an anti-diabetic drug, is known to have anti-tumor effects. We examined the outcome of 177 patients with type 2 diabetes mellitus (T2DM) who received surgery for breast cancer. Among them, 49 patients were treated with drugs including metformin. In those patients, recurrence in distant organs was less frequent and postoperative disease-free survival (DFS) tended to be better than those without metformin intake. In patients who received preoperative systemic therapy (PST), rate of pathological complete response (pCR) was significantly more frequent in patients with metformin treatment (p &amp;lt; 0.05). Multiplex immunohistochemical staining of resected tumors revealed that the density of tumor associated macrophages (TAM), especially of CD68(+)CD163(+) M2-type TAM, was significantly lower in tumors with metformin treatment. In contrast, the rate of CD8(+) phenotype in CD3(+) tumor infiltrating lymphocytes (TILs) was significantly higher in metformin group. The results suggest that metformin can change the immune microenvironment from pro-tumorigenic to anti-tumorigenic status, which leads to the favorable outcome of the patients with breast cancer and T2DM. Citation Format: Satomi Shiba, Michiko Harao, Kasumi Ogihara, Takayo Fukuda, Masako Sakuragi, Kitayama Joji, Naohiro Sata. Metformin may improve the outcome of patients with breast cancer and type 2 diabetes mellitus through the effect of tumor immune microenvironment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-08-06.

High-risk Patients With Colorectal Liver Metastases Assessed by the Beppu Score Can Have Excellent Survival Through Multidisciplinary Treatment Including Local Ablation.

The Beppu score assessed by the Japanese Society of Hepato-Biliary-Pancreatic Surgery nomogram helps predict postoperative disease-free survival for patients with resectable colorectal liver metastases (CRLM). Using the Beppu score, patients with resectable CRLM were divided into three groups according to recurrence risk: low (≤6 points), moderate (7-10 points), and high-risk (≥11 points). Hepatectomy following preoperative chemotherapy is recommended for high-risk patients. The surgical outcome, local recurrence rates, and long-term survival were assessed, focusing on local ablation. Twenty high-risk and unresectable CRLM patients were enrolled between April 2016 and April 2022. Hepatectomy with or without local ablation was performed after induction chemotherapy. Local ablation was permissive for patients with effective chemotherapy (partial response and stable disease) with CRLM ≤2 cm and ≥5 mm distant from major vessels. The median diameters and numbers of CRLM were 26 (10-150) mm and 9 (1-46). All 18 patients who received preoperative chemotherapy were disease controls. Local ablation was performed simultaneously on hepatectomy in 14 patients. The median diameters and numbers of the ablated nodules were 12 (5-17) mm and 3 (1-21). Local recurrence was 8.5% per 82 ablative nodules. Three-year disease-free and five-year overall survival was 57.4% and 56.2%, respectively. There was no significant difference in patients with or without local ablation. Our treatment strategy for high-risk CRLM patients is feasible and can provide an excellent long-term prognosis regardless of adding local ablation to hepatectomy.

Molecular mechanism of formation and destruction of a pseudo‑capsule in clear cell renal cell carcinoma.

The process and molecular mechanisms underlying the formation and destruction of a pseudo-capsule (PC) in clear cell renal cell carcinoma (ccRCC) are poorly understood. In the present study, the PCs of surgical specimens from primary tumors and metastatic lesions in 169 patients with ccRCC, and carcinogen-induced ccRCC rat models were semi-quantified using the invasion of PC (i-Cap) score system. This was based on the relationship among the tumor, PC and adjacent normal tissue (NT) as follows: i-Cap 0, tumor has no PC and does not invade NT; i-Cap 1, tumor has a complete PC and does not invade into the PC; i-Cap 2, tumor with focal absences in the PC, which partially invades the PC but not completely through the PC; i-Cap 3, tumor crosses the PC and invades the NT; i-Cap 4, tumor directly invades the NT without a PC. The study suggested that PC formation was not observed without physical compression, and also revealed that tumor invasion into the PC was a prognostic factor for postoperative oncological outcomes. Higher i-Cap, Fuhrman grade and tumor size were independent poor prognostic factors for postoperative disease-free survival. mRNA expression arrays generated from carcinogen-induced ccRCC rat models were used to explore genes potentially associated with the formation and destruction of a PC. Subsequently, human ccRCC specimens were validated for four genes identified via expression array; the results revealed that collagen type 4A2, matrix metalloproteinase-7 and l-selectin were upregulated alongside the progression of i-Cap score. Conversely, endoglin was downregulated. In conclusion, the present study provides insights into the formation and destruction of a PC, and the results may aid the treatment and management of patients with ccRCC.

Systemic Chemotherapy in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery: Systematic Review and Meta-Analysis.

For patients with colorectal cancer (CRC) peritoneal metastases (PM) who are eligible for cytoreductive surgery (CRS), the indication and timing of systemic chemotherapy (SC) are still under debate. This study aims to analyze the role of pre, post or perioperative SC on the survival and surgical complications of patients treated with CRS-HIPEC. After a systematic search in MEDLINE, Cochrane Database of Systematic Reviews, Scopus, Web of Science and Embase, a meta-analysis was performed to compare postoperative complications, disease-free survival (DFS) and overall survival (OS) according to SC administration and timing. CRD42023478977. Of 1203 studies screened, 15 were included in the meta-analysis (4523 patients). Post-operative SC was associated with increased overall survival (post-SC vs. no post-SC: HR 0.81, p = 0.00001, I2 = 0%; pre-SC vs. post-SC: HR 0.65, p = 0.01, I2 = 28%), whereas SC (pre or post) or pre-SC compared to surgery alone was not (SC vs. no SC: p = 0.29, I2 = 80%; pre-SC vs. no pre-SC: p = 0.59, I2 = 58%). Similar results were seen for DFS. SC was not associated with an increased complication rate (p = 0.47, I2 = 64%). Systemic chemotherapy administration in patients undergoing radical surgery for colorectal peritoneal metastases is associated with increased survival only in the adjuvant/post-operative setting. Considering the limitations of the included studies, further trials are needed to answer this unresolved question.

UroPredict: Machine learning model on real-world data for prediction of kidney cancer recurrence (UroCCR-120)

Renal cell carcinoma (RCC) is most often diagnosed at a localized stage, where surgery is the standard of care. Existing prognostic scores provide moderate predictive performance, leading to challenges in establishing follow-up recommendations after surgery and in selecting patients who could benefit from adjuvant therapy. In this study, we developed a model for individual postoperative disease-free survival (DFS) prediction using machine learning (ML) on real-world prospective data. Using the French kidney cancer research network database, UroCCR, we analyzed a cohort of surgically treated RCC patients. Participating sites were randomly assigned to either the training or testing cohort, and several ML models were trained on the training dataset. The predictive performance of the best ML model was then evaluated on the test dataset and compared with the usual risk scores. In total, 3372 patients were included, with a median follow-up of 30 months. The best results in predicting DFS were achieved using Cox PH models that included 24 variables, resulting in an iAUC of 0.81 [IC95% 0.77–0.85]. The ML model surpassed the predictive performance of the most commonly used risk scores while handling incomplete data in predictors. Lastly, patients were stratified into four prognostic groups with good discrimination (iAUC = 0.79 [IC95% 0.74–0.83]). Our study suggests that applying ML to real-world prospective data from patients undergoing surgery for localized or locally advanced RCC can provide accurate individual DFS prediction, outperforming traditional prognostic scores.

Influence of skeletal muscle and intermuscular fat on postoperative complications and long-term survival in rectal cancer patients.

The body composition of patients with rectal cancer potentially affects postoperative outcomes. This study explored the correlations between skeletal muscle and adipose tissue quantified by computed tomography (CT) with postoperative complications and long-term prognosis in patients with rectal cancer after surgical resection. This retrospective cohort study included patients with rectal cancer who underwent surgical resection at the Wuhan Union Hospital between 2014 and 2018. CT images within 3months prior to the surgery were used to quantify the indices of skeletal muscle and adipose tissue at the levels of the third lumbar vertebra (L3) and umbilicus. Optimal cut-off values for each index were defined separately for males and females. Associations between body composition and postoperative complications, overall survival (OS), and disease-free survival (DFS) were evaluated using logistic and Cox proportional hazards models. We included 415 patients (240 males and 175 females; mean age: 57.8±10.5years). At the L3 level, a high skeletal muscle density (SMD; hazard ratio [HR]: 0.357, 95% confidence interval [CI]: 0.191-0.665, P=0.001; HR: 0.571, 95% CI: 0.329-0.993, P=0.047) and a high skeletal muscle index (SMI; HR: 0.435, 95% CI 0.254-0.747, P=0.003; HR: 0.568, 95% CI: 0.359-0.897, P=0.015) were independent prognostic factors for better OS and DFS. At the umbilical level, a large intermuscular fat area (IMFA; HR: 1.904, 95% CI: 1.068-3.395, P=0.029; HR: 2.064, 95% CI: 1.299-3.280, P=0.002) was an independent predictive factor for worse OS and DFS, and a high SMI (HR: 0.261, 95% CI: 0.132-0.517, P<0.001; HR: 0.595, 95% CI: 0.387-0.913, P=0.018) was an independent prognostic factor for better OS and DFS. The models combining body composition and clinical indicators had good predictive abilities for OS. The receiver operating characteristic areas under the curve were 0.848 and 0.860 at the L3 and umbilical levels, respectively (both P<0.05). No correlations existed between CT-quantified body composition parameters and postoperative complications. However, a high SMD and high SMI were significantly associated with longer OS and DFS at the L3 level, whereas a large IMFA and low SMI were associated with worse OS and DFS at the umbilical level. Combining CT-quantified body composition and clinical indicators could help physicians predict the prognosis of patients with rectal cancer after surgery.

Recurrence-risk stratification using the Beppu score and selection of perioperative chemotherapy for colorectal liver metastases.

The annual postoperative disease-free survival for colorectal liver metastases can be easily estimated by weighting six preoperative clinical parameters (Beppu score). We identified three recurrence-risk stratification groups: the low (≤6 points), moderate (7-10 points), and high-risk (≥11 points). For low-, moderate-, and high-risk patients, hepatectomy alone, hepatectomy with adjuvant chemotherapy, and hepatectomy with preoperative chemotherapy are recommended, respectively. The Beppu score enables the decision on the necessity and timing of perioperative chemotherapy.

Predictive value of Global Leadership Initiative on Malnutrition criteria combined with handgrip strength for postoperative outcomes in overweight colorectal cancer patients.

The Global Leadership Initiative on Malnutrition (GLIM) criteria are increasingly used to assess the nutritional status of hospitalized patients and predict the prognosis of patients with malignant tumors; however, malnutrition is often overlooked in overweight individuals, such as colorectal cancer patients. This study aimed to investigate the predictive value of the GLIM criteria combined with handgrip strength (HGS) in overweight colorectal cancer patients. This retrospective study enrolled overweight patients who underwent radical resection for colorectal cancer at two centers between 2015 and 2021. Malnutrition was diagnosed based on the GLIM criteria. Skeletal muscle mass was assessed using the skeletal muscle index, and skeletal muscle function was assessed using the HGS test. The risk factors for complications and survival were also evaluated. A total of 850 patients were enrolled in the study. The incidence of malnutrition in the GLIM and HGS-GLIM groups was 12.4% and 6.4%, respectively. The incidence of total complications in both the malnutrition groups was significantly higher than that in the control group. Patients in the HGS-GLIM-malnutrition group had worse overall survival and disease-free survival. HGS-GLIM was independently associated with postoperative complications (P=0.046), overall survival (P=0.037), and disease-free survival (P=0.047). The GLIM criteria combined with the HGS test is an effective tool for diagnosing malnutrition. Particularly, these modalities are applicable in overweight colorectal cancer patients. Compared with the standard GLIM criteria, this tool has a better predictive value for postoperative complications and long-term survival.

The impact of the highest mediastinal lymph node metastasis on postoperative recurrence and survival in non-small cell lung cancer patients

Objective: To examine whether the highest mediastinal lymph node (HMLN) metastasis had an influence on postoperative recurrence and survival among non-small cell lung cancer (NSCLC) patients with pN2 lymph node metastasis. Methods: A total of 261 patients who underwent radical resection of lung cancer and systematic lymph node dissection in the Department of Thoracic Surgery of Peking University First Hospital from January 2007 to December 2016 were retrospectively analyzed. There were 180 males and 81 females, aged (61.5±9.4) years (range: 31 to 83 years). There were 128 cases of HMLN-positive and 133 cases of HMLN-negative. They were pathologically confirmed N2 stage NSCLC and postoperative recurrence and survival were followed up. The Kaplan-Meier method was used to calculate disease-free survival (DFS) and overall survival (OS) curves according to whether HMLN metastasize or not. The Cox proportional hazards regression model was used for the prognostic analysis. Results: The median DFS and the median OS of the whole group were 28 months and 44 months, respectively. The median DFS in HMLN-positive and HMLN-negative patients was 19 months and 33 months, respectively (P=0.005). The median OS of HMLN-positive and HMLN-negative group was 37 months and 49 months, respectively (P=0.005). Multivariate analysis showed that pneumonectomy and visceral pleural invasion were independent risk factors for both postoperative OS (HR=1.85, 95%CI: 1.25 to 2.72, P=0.002; HR=1.82, 95%CI: 1.30 to 2.56, P=0.007) and DFS (HR=1.61, 95%CI: 1.10 to 2.35, P=0.014; HR=1.77, 95%CI: 1.27 to 2.46,P=0.001). HMLN metastasis and lymphovascular invasion were independent risk factors for only postoperative DFS (HR=1.39, 95%CI: 1.03 to 1.87, P=0.030; HR=1.40, 95%CI: 0.99 to 1.81, P=0.042). Conclusions: For patients of pN2 stage NSCLC, both postoperative recurrence and long-term survival were significantly worse in the HMLN metastatic group. In addition, pneumonectomy and visceral pleural invasion were unfavorable factors that affected both recurrence and overall survival. HMLN metastasis and lymphovascular invasion could shorten the postoperative time for DFS.

Sarcopenia predicts postoperative complications and survival in colorectal cancer patients with GLIM-defined malnutrition: Analysis from a prospective cohort study

ObjectiveTo investigate whether sarcopenia could predict postoperative outcomes in patients with colorectal cancer with Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition. MethodsClinical data of patients who underwent radical resection for colorectal cancer were prospectively collected. Sarcopenia was diagnosed by the combination of low handgrip strength and low muscle quantity or quality as measured by abdominal computed tomography (CT) images. Logistic regression analysis and Cox proportional hazards regression analysis were performed to identify independent predictors for postoperative complications and survival, respectively. ResultsA total of 310 patients with colorectal cancer with GLIM-defined malnutrition were included, of which 145 (46.77%) were identified with sarcopenia. Malnutritional patients with sarcopenia had significantly higher incidences of total complications (34.5% versus 15.8%), severe complications (9.7% versus 1.8%), longer lengths of postoperative hospital stay (median, 14 days versus 12 days), and more costs (median, 56,257 RMB versus 49,024 RMB) than those without sarcopenia. Sarcopenia was an independent predictive factor for postoperative complications (OR 2.531, 95% CI 1.451–4.415), overall survival (HR 1.519, 95% CI 1.026–2.248), and disease-free survival (HR 1.847, 95% CI 1.324–2.576). Patients with severe sarcopenia had a higher incidence of severe complications but not total complications or survival than those with not-severe sarcopenia. Moreover, the predictive value of sarcopenia for postoperative complications was attributed to muscle strength and quality but not muscle quantity. ConclusionSarcopenia predicts postoperative complications and survival in patients with colorectal cancer with GLIM-defined malnutrition. Preoperative assessment of sarcopenia is still necessary when nutritional assessment has been well performed.

A comparative study of clinicopathological and imaging features of HBV-negative and HBV-positive intrahepatic cholangiocarcinoma patients with different pathologic differentiation degrees

Hepatitis B is a risk factor for the development of intrahepatic cholangiocarcinoma. The prognosis of HBV-related ICC remains to be further investigated. To investigate the clinical, pathological and imaging features of intrahepatic cholangiocarcinoma of hepatitis B virus-positive and -negative patients. Data from January 31, 2012 to December 31, 2019 of 138 patients were retrospectively analyzed. The patients were divided into hepatitis B virus-positive group (group A[n = 66]) and virus-negative group (group B[n = 72]), and the patients were divided into groups according to pathological differentiation degree and tumor size. The differences in clinical, imaging characteristics and the progression-free survival between groups were analyzed. There were significant differences in gender, age, HBc antibody, CA125 and AFP, tumor distribution site, maximum diameter, plain scan density, inferior hepatic angle, peritumoral bile duct dilatation, vascular encasement invasion, intrahepatic bile duct dilatation and lymphadenopathy between the two groups (P < 0.05); There were statistical differences in signs of vascular encasement invasion between the two groups with well-to-moderately differentiated tumors (P < 0.05); there were statistical differences in tumor density uniformity, signs of vascular encasement invasion and lymphadenopathy between the two groups with poorly differentiated tumors (P < 0.05). Large groups A and B showed differences in tumor density uniformity, vascular encasement invasion, arterial phase, overall reinforcement pattern, peritumoral bile duct stones and biliary dilatation (P < 0.05). There was no statistical difference in postoperative PFS between the two groups (P > 0.05). The clinical and imaging features of ICC of hepatitis B virus-positive and -negative patients are different, and there is little difference in postoperative disease-free survival time.

Randomised, placebo-controlled, phase 3 trial of the effect of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on colorectal cancer recurrence and survival after surgery for resectable liver metastases: EPA for Metastasis Trial 2 (EMT2) study protocol

IntroductionThere remains an unmet need for safe and cost-effective adjunctive treatment of advanced colorectal cancer (CRC). The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and has anti-inflammatory...

Anastomotic leakage and functional outcomes following total mesorectal excision with delayed and immediate colo-anal anastomosis for rectal cancer: Two single-arm phase II trials

BackgroundAnastomotic leakage (AL) remains a major cause of morbidity following total mesorectal excision (TME). A diverting ileostomy reduces the risk of AL but impairs quality of life (QoL). Delayed colo-anal anastomosis (DCAA) may be an alternative to immediate colo-anal anastomosis (ICAA) without creation of a diverting ileostomy. Study designPatients with T3 or N+ rectal tumours were treated with neoadjuvant chemoradiation and TME. To evaluate DCAA or ICAA with diverting ileostomy, a two multicenter single-arm phase II trials was designed. The primary endpoint was the rate of AL requiring a diverting ileostomy up to 30 days postoperatively. Secondary endpoints were 30-day postoperative complications, 1- and 2-year disease-free survival; QoL at baseline, 6 months and anorectal function measured by the low anterior resection syndrome questionnaire and Wexner score at baseline, 6 months and a late assessment at median 8 years following surgery. ResultsAL requiring diverting ileostomy occurred in one patient (2.1%; 95% confidence interval (CI) [0; 11.1]) in the DCAA group and in five patients (8.6%; 95%CI [3.2; 21.0]) in the ICAA group. Thirty-day postoperative complications occurred in 13 patients (27.1%) in the DCAA group and in 10 patients (19.2%) in the ICAA group. Short and long-term functional outcomes showed similar patterns. ConclusionThese two single-arm phase II trials showed that DCAA has low rates of AL requiring a diverting ileostomy and acceptable long-term functional results. DCAA seems a good choice to restore bowel continuity.

Cyclin A1 affects the invasion, metastasis, and prognosis of hepatocellular carcinoma

Objective: To investigate the effect of cyclin A1 on the invasion, metastasis, and prognosis of hepatocellular carcinoma (HCC). Methods: Immunohistochemistry (IHC) was used to detect the expressional condition of cyclin A1 in HCC and paraffin-embedded non-tumor adjacent tissues. Kaplan-Meier method was used for the survival analysis of patients with HCC. Western blot (WB) was used to detect the expression of cyclin A1 in HCCLM3 and QGY-7703 cells. Scratch wound healing assay, transwell migration, and invasion assay were used to detect the effect of cyclin A1 overexpression on cell migration and invasion ability. WB was used to detect changes in the expression of matrix metalloproteinase (MMP) 2, MMP9, and vascular endothelial growth factor (VEGF) after overexpression of cyclin A1. Measurement data were compared using a t-test and analysis of variance. Count data was measured using χ (2) test and the Log-rank method was performed for survival analysis. Results: Cyclin A1 expression rates were higher in the tissues of HCC patients with recurrent metastasis than in the tissues of patients without recurrent metastasis (60.42% vs. 46.81%, χ (2) = 4.711, P < 0.05). The overall postoperative survival time (OS) and disease-free survival (DFS) were shorter in patients with high cyclin A1 expression than those with low cyclin A1 expression (45.9 months vs. 53.1 months; 42.9 months vs. 51.3 months, and P < 0.01). The postoperative OS and DFS were shorter in patients with high cyclin A1 expression and recurrent metastasis than those with low cyclin A1 expression without recurrent metastasis (31.7 months vs. 43.9 months; 18.0 months vs. 31.5 months, and P < 0.05). HCCLM3 and QGY-7703 cells were higher in the cyclin A1-pEX group than in the empty vector (vector) group (1.56 ± 0.06 vs. 0.18 ± 0.01, t = 18.75, P < 0.001; 1.31 ± 0.05 vs.0.37 ± 0.02, t = 15.17, P < 0.001). The migrated distances of HCCLM3 cells in the cyclin A1-pEX group and the vector group were (536.7 ± 14.5) μm and (327.3 ± 9.3) μm, t = 11.84, P < 0.05, respectively, while the migrated distances of QGY-7703 cells in the two groups were (916.7 ± 35.3) μm and (320.0 ± 20.8) μm, t = 13.54, P < 0.01. The migrated numbers of HCCLM3 cells in the cyclin A1-pEX group and vector group were (37.3 ± 2.4) and (7.0 ± 1.2), t = 12.67, P < 0.001, and the number of invasive cells was (73.7 ± 4.1) and (12.6 ± 1.5), t = 12.36, P < 0.001, respectively. The migrated numbers of QGY-7703 cells in the two groups were (153.3 ± 6.0) and (17.7 ± 3.7), t = 17.59, P < 0.001, and the number of invasive cells was (45.0 ± 2.9) and (9.3 ± 1.5), t = 10.66, P < 0.001, respectively. The expression levels of MMP2, MMP9, and VEGF in HCCLM3 and QGY-7703 cells were significantly higher in the cyclin A1-pEX group than those in the vector group (P < 0.05). Conclusion: Cyclin A1 plays an important role in HCC invasion and metastasis, but HCC patients with high cyclin A1 expression have a poor prognosis. Hence, cyclin A1 has high guiding significance for evaluating patient prognosis.

Correlation analysis of hemoglobin, albumin, lymphocyte, platelet score and platelet to albumin ratio and prognosis in patients with lung adenosquamous carcinoma.

To investigate the effect of hemoglobin, albumin, lymphocytes, platelet (HALP) score and platelet to albumin ratio (PAR) on prognosis of patients with lung adenosquamous carcinoma (ASC) after surgery. A total of 52 patients diagnosed with ASC after surgical resection were collected from Nanjing Chest Hospital from 2012 to 2021, and their general clinical data, pathological data and laboratory indexes were collected. The changes of Alb and Plt levels before and after surgery, HALP scores (hemoglobin albumin lymphocytes/platelets), and postoperative PAR, PLR, NLR were retrospectively analyzed, and their influence on the prognosis of patients with ASC was investigated. The cut-off value of △Alb, △Plt, postoperative PAR, PLR and NLR were determined by the receiver operating characteristic (ROC) curve, the optimal cut-off value of HALP score before and after surgery was calculated by using X-tile software, and the clinicopathological characteristics were compared between the high PAR and low PAR groups and between high HALP score and low HALP score group to analyze the factors influencing the prognosis of patients with ASC. Univariate and multivariate Cox proportional regression analyses were used to assess independent risk factors affecting overall survival (OS) and disease-free survival (DFS) in patients with ASC. Kaplan-Meier method was used to evaluate the correlation between OS, DFS and PAR and HALP score. A critical value of PAR was 7.40×10^9 and an area under the curve (AUC) of 0.737 (95%CI: 0.597-0.876, P = 0.004). The best cut-off value of the preoperative HALP score was 24.3. Univariate Cox analysis showed that the cut margin (P = 0.013), the degree of differentiation (P = 0.021), N stage (P = 0.049), △Plt (P = 0.010), △Alb (P = 0.016), PAR (P = 0.003), NLR (P = 0.025), PLR (P = 0.029), preoperative HALP score (P = 0.000) and post-operative HALP score (P = 0.010) were all associated with postoperative OS in ASC patients. Cut margin (P = 0.029), the degree of differentiation (P = 0.045), maximum tumor diameter (P = 0.018), N stage (P = 0.035), △Plt (P = 0.007), △Alb (P = 0.007), PAR (P = 0.004), NLR (P = 0.041), PLR (P = 0.030), preoperative HALP score (P = 0.000), and postoperative HALP score (P = 0.011) were related to postoperative DFS in ASC patients. Multivariate analysis revealed that PAR (HR: 6.877, 95%CI: 1.817-26.038, P = 0.005), differentiation degree (HR: 0.059, 95%CI: 0.006-0.591, P = 0.016) and preoperative HALP score (HR: 0.224, 95%CI: 0.068-0.733, P = 0.013) had significant effect on OS. Tumor maximum diameter (HR: 3.442, 95%CI: 1.148-10.318, P = 0.027) and preoperative HALP score (HR: 0.268, 95%CI: 0.085-0.847, P = 0.025) had significant influence on DFS. PAR and preoperative HALP score were potentially useful biomarkers for evaluating the outcome of patients with postoperative ASC. PAR, the degree of differentiation and preoperative HALP score were independent prognostic factors for postoperative OS in ASC patients. Maximum tumor diameter and preoperative HALP score were independent prognostic factors for postoperative DFS in ASC patients.

Inverse probability of treatment weighting analysis of laparoscopic versus open Sg4b-5 bi-segmentectomy in patients with gallbladder cancer.

Sg4b-5 anatomical bi-segmentectomy with regional lymphadenectomy (Sg4b5) is a surgical option for gallbladder cancer (GBC) treatment. The laparoscopic approach to this challenging operation is still controversial. Aim of this study was to compare short- and long-term outcomes of laparoscopic versus open Sg4b5 in a single institution series of patients. All consecutive patients who underwent Sg4b5 for GBC from January 2000 to September 2021 were retrospectively reviewed. Inverse probability of treatment weighting (IPTW) analysis was performed. 75 patients were analyzed, 18 in the laparoscopic and 57 in the open group. After IPTW, laparoscopic approach was associated with a significantly decreased median intraoperative blood loss (100 vs 237.09ml, p = 0.001), shorter median length of hospital stay (4 vs 8days, p = < 0.001) and a higher median number of harvested nodes (9 vs 7, p = 0.026). Operation time was shorter in the open group (355 vs 259min, p < 0.001). No significant differences were found regarding clear resection margins, overall and major (Clavien-Dindo ≥ 3) morbidity, bile leakage rate, 90days post-operative mortality, overall and disease-free survival. Laparoscopic Sg4b-5 anatomical bi-segmentectomy and regional lymphadenectomy is feasible and safe with long term outcome comparable to open approach at least in early stages. Laparoscopic approach confirms its well-known short-term benefits with less intraoperative bleeding and shorter length of stay. Moreover, it might allow a better lymphadenectomy.

Expression of fibroblast growth factor receptor substrate 2 (FRS2) in primary retroperitoneal liposarcoma and its clinical implications.

The aim of this study was to investigate the expression level of fibroblast growth factor receptor substrate 2 (FRS2) in tissues of patients with primary retroperitoneal liposarcoma (PRPLS) and its correlation with recurrence and prognosis. The pathological specimens, medical records, and follow-up information of patients with PRPLS who underwent radical surgery for the first time in our hospital from January 2013 to December 2016 were retrospectively analyzed. FRS2 protein expression in tissues was determined by immunohistochemistry staining, and the FRS2 protein positive rates in patients with different clinicopathological features were compared. Factors influencing patients' recurrence and survival were determined using the multivariate Cox stepwise regression model. This research enrolled 87 patients with PRPLS, with the number of cases presenting FRS2 protein positive rate and positive rate in pathological tissues accounting for 62.07% (54/87) and 37.93% (33/87), respectively. The positive expression of FRS2 protein varied markedly among patients with different pathological types, FNCC, LCC grade, number of tumors, positive margin, and recurrence and metastasis (with vs. without) (all p<0.05). The 87 patients were followed up for 3.5-102 months (median, 27.5 months), with a postoperative 5-year overall disease-free survival (DFS) rate of 17.24% [median progression-free survival (PFS): 24.7 months] and a 5-year overall survival (OS) rate of 44.83% (median OS: 47.3 months). Kaplan-Meier survival curves revealed significantly shorter PFS and OS in patients with positive FRS2 protein expression vs. those with negative FRS2 protein expression (χ2=6.396, 5.032, p<0.05). According to the univariate analysis, the 5-year overall DFS rate varied significantly among patients with different pathological types, Fédération Nationale des Centres De Lutte Contre le Cancer (FNCLCC) grades, number of tumors, positive margin, and FRS2 protein expression (all p<0.05). Pathological type, FNCLCC grading, tumor number, recurrence and metastasis, positive margin, and FRS2 protein expression were significantly correlated with the 5-year OS rate of patients (all p<0.05). Furthermore, pathological type, FNCLCC grading, multiple tumors, positive margin, and FRS2 protein expression were identified by multivariate Cox regression analysis to be independent factors that affected patients' 5-year DFS and OS rates (all p<0.05), and that relapsed and metastasized patients had a 4.586-fold risk of death than those without recurrence and metastasis. FRS2 shows a high positive rate in the tissues of PRPLS patients and is significantly related to the prognostic recurrence and survival of patients, with potential value in judging the prognosis of patients.

Impact of Aspirin Intake on Postoperative Survival after Primary Pancreatic Resection of Pancreatic Ductal Adenocarcinoma-A Single-Center Evaluation.

(1) Background: The intake of aspirin (ASS) has been demonstrated to have a relevant impact on the pathogenesis, incidence and outcome in different solid gastrointestinal tumors. However, data on the effect of ASS on the short-term outcome and the long-term survival in patients with pancreatic carcinoma are still limited. (2) Methods: A total of 213 patients who underwent primary resection of PDAC at the University Hospital of Erlangen from January 2000 to December 2018 were included in this retrospective single-center study in total. Patients were stratified according to the aspirin intake into three groups: continuous aspirin intake (cASS), perioperatively interrupted aspirin intake (iASS) and no aspirin intake (no ASS) at the timepoint of surgery. The postoperative outcome as well as long-term survival were compared between the groups. (3) Results: There were no differences regarding postoperative morbidity (iASS: 54% vs. cASS: 53% vs. no ASS: 64%, p = 0.448) and in-hospital mortality (iASS: 4% vs. cASS: 10% vs. no ASS: 3%, p = 0.198) between the groups. The overall survival (OS) and disease-free survival (DFS) did not differ in the groups when comparing the ASS-intake status (OS: iASS 17.8 months vs. cASS 19.6 months vs. no ASS 21.6 months, p = 0.489; DFS: iASS 14.0 months vs. cASS 18.3 months vs. no ASS 14.7 months, p = 0.957). Multivariate analysis revealed that age (hazard ratio (HR) 2.2, p < 0.001), lymph node-positive status (HR 2.0, p < 0.001), R status 1 or 2 (HR 2.8, p < 0.001) and differentiation with a grading of 3 (HR 1.7, p = 0.005) were significant independent prognostic factors regarding the OS. Moreover, age (HR 1.5, p = 0.040), lymph node-positive status (HR 1.8, p = 0.002) and high-grade (G3) carcinomas (HR 1.5, p = 0.037) could be identified as independent prognostic parameters for DFS. (4) Conclusions: In patients undergoing primary surgery for curative resection of pancreatic carcinoma, the perioperative intake of ASS had no significant impact on postoperative outcome, overall and disease-free survival.