Risk Factors For Tumor Recurrence Research Articles

Growth differentiation factor 7 alleviates the proliferation and metastasis of hepatocellular carcinoma

Background and aimInflammatory factors play significant roles in the development and occurrence of hepatocellular carcinoma (HCC). However, the tumor-protective functions of growth differentiation factors (GDFs) in HCC are yet to be clarified. In this study, we aimed to evaluate the expression levels of 10 GDFs in tumor and paratumor tissues from patients with HCC and perform in vitro and in vivo experiments to elucidate the role of GDF7 in regulating the proliferation and metastasis of HCC. MethodsThe gene expression of 10 GDFs was compared between HCC and paratumors using The Cancer Genome Atlas dataset and patient-derived tissues. A tumor microarray containing 108 HCC tissue samples was used to explore the prognostic value of GDF7 expression. Loss-of-function experiments were also performed in vitro and in vivo to investigate the role of GDF7 in HCC. ResultsThe mRNA and protein levels of GDF7 were significantly lower in HCC tumors than in paratumors (P < 0.001). Kaplan–Meier analysis showed that decreased GDF7 expression in HCC was associated with worse overall survival (5-year rate: 61.8% vs. 27.5%, P < 0.001) and increased recurrence risk (P < 0.001). Multivariate Cox regression analysis demonstrated that low GDF7 expression, the presence of microvascular invasion, and elevated alpha-fetoprotein (AFP) levels were independent risk factors for tumor recurrence and poor survival. Downregulation of GDF7 also increased the tumor growth in HCC cells and in an HCC xenograft model. GDF7 knockdown promoted migration and invasion via epithelial–mesenchymal transition. Meanwhile, a negative correlation between JunB proto-oncogene (JUNB) and GDF7 was observed in HCC tissues. Modulating JUNB levels altered GDF7 protein expression. ConclusionGDF7 is a potential biomarker for predicting superior outcomes in patients with HCC. GDF7 amplification is a potential therapeutic option for HCC.

Prognostic Implications of Maintaining the Target Thyroid-Stimulating Hormone Status Based on the 2015 American Thyroid Association Guidelines in Patients with Low-Risk Papillary Thyroid Carcinoma after Lobectomy: A 5-Year Landmark Analysis

Background: The 2015 American Thyroid Association guidelines recommend the maintenance of serum thyroid stimulating hormone (TSH) levels ≤2 mIU/L in patients with low-risk papillary thyroid carcinoma (PTC) who underwent lobectomy; however, the evidence is insufficient. We investigated the association between maintaining the TSH status at ≤2 mIU/L and tumor recurrence in patients with low-risk PTC who underwent lobectomy through a 5-year landmark analysis. Methods: Between 2010 and 2016, 662 patients with low-risk PTC were included. The postoperative TSH status was determined using the ‘TSH &gt; 2 ratio’, which was calculated using the TSH test results during the 5-year follow-up. The optimal cutoff value of ‘TSH &gt; 2 ratio’ for tumor recurrence was determined using a receiver operating characteristic curve analysis. Recurrence-free survival (RFS) was compared between the groups using Kaplan–Meier and Cox proportional hazard regression analyses. Results: Patients with ‘TSH &gt; 2 ratio’ &gt; 0.1833 (n = 498) had a worse RFS outcome compared to patients with ‘TSH &gt; 2 ratio’ ≤ 0.1833 (n = 164; p &lt; 0.001). ‘TSH &gt; 2 ratio’ &gt; 0.1833 was a significant risk factor for tumor recurrence after the 5-year landmark (hazard ratio: 4.795, 95% confidence interval: 2.102–10.937, p &lt; 0.001). Conclusions: Maintaining TSH levels ≤ 2 mIU/L below a certain percentage among the total TSH tests during the 5-year follow-up period has a negative impact on tumor recurrence.

Association between Thyroid Profile Levels and Lymph Node Metastasis in Papillary Thyroid Carcinoma: A Retrospective Study

Background: Thyroid cancer is the most common endocrine carcinoma, accounting for 3.26% of all cancers. The most histologically, well-differentiated thyroid cancer is papillary thyroid carcinoma (PTC). Although PTC is regarded as an indolent tumor, a portion of the cancer cells metastasize to lymph nodes around the thyroid gland. Lymph node metastasis (LNM) is a critical risk factor for tumor recurrence in PTC, which strongly affects disease prognosis and the quality of life. Methods: This study aims to examine how differences in the level of the thyroid profile and other risk factors may influence LNM incidence in patients with PTC in Taiwan. We carried out a single-center retrospective study. These PTC patients were retrospectively reviewed by the Department of Endocrinology from 2016 to 2019. A total of 165 patients were included in our research. Results: The findings revealed a close relationship with the level of free thyroxine (FT4), the level of the thyroid-stimulating hormone (TSH), and lymph node metastases. The correlation in terms of FT4 (p = 0.005) and TSH (p = 0.417) with LNM was found as a result of the univariate regression analysis. In the multiple regression analysis, the findings revealed a close relationship between LNM, FT4 (p &lt; 0.001), and TSH (p = 0.008). Conclusions: Although the predictability of the TSH should be examined further, the association between LNM and FT4 or TSH should not be ignored. The results could help guide decision-making and patient counseling, using the level of serum FT4 or the TSH as a possible predictive factor of the LNM in PTC.

Increasing monocytes after lung cancer surgery triggers the outgrowth of distant metastases, causing recurrence

Patients with lung cancer have a high incidence of tumor recurrence even after curative surgical resection. Some reports indicated that immunosuppressive cells induced by surgical stress could contribute to tumor recurrence after surgery; however, the underlying mechanisms are not fully understood. In this study, we found that increased postoperative blood monocytes served as a risk factor for tumor recurrence in 192 patients with non-small cell lung cancer (NSCLC). We established the lung cancer recurrent mouse model after tumor resection and showed that the surgical stress immediately increased the level of serum monocyte chemoattractant protein-1 (MCP-1), which subsequently increased blood monocytes. These blood monocytes were rapidly recruited into distant micrometastases and became tumor growth-promoting tumor associated macrophages (TAMs). Furthermore, even after the blood MCP-1 and monocytes decreased enough 72 h after tumor resection, TAMs in micrometastases remained rich because the MCP-1 secreted by micrometastases themselves continued to recruit monocytes around the tumor. Consequently, tumor resection triggered the outgrowth of distant metastases via the MCP-1–Monocyte–TAM axis. When we administered the MCP-1 inhibitor to the lung cancer recurrent model mice, blood monocytes decreased after tumor resection, and TAMs in micrometastases also dramatically decreased. Finally, peri- and postoperative treatment with the MCP-1 inhibitor suppressed distant metastases after surgery. Targeting the MCP-1–Monocyte–TAM axis may inhibit surgical stress-induced NSCLC recurrence by attenuating postoperative immunosuppressive monocytes in micrometastases.

Does autoimmune disease impair the survival of hepatocellular carcinoma patients undergoing liver resection? A multi-institutional observational study

BackgroundPatients with autoimmune diseases (AD) generally carry an increased risk of developing cancer. However, the effect of AD in hepatocellular carcinoma (HCC) patients receiving surgical treatment is uncertain. The present study aimed to investigate the potential influence of AD on the survival of HCC patients undergoing hepatectomies.MethodsOperated HCC patients were identified from the Chang Gung Research Database, and the survival outcomes of HCC patients with or without AD were analyzed ad compared. Cox regression model was performed to identify significant risk factors associated with disease recurrence and mortality.ResultsFrom 2002 to 2018, a total of 5532 patients underwent hepatectomy for their HCC. Among them, 229 patients were identified to have AD and 5303 were not. After excluding cases who died within 30 days of surgery, the estimated median overall survival (OS) was 43.8 months in the AD (+) group and 47.4 months in the AD (–) group (P = 0.367). The median liver-specific survival and disease-free survival (DFS) were also comparable between the two groups. After Cox regression multivariate analysis, the presence of AD did not lead to a higher risk of all-cause mortality, liver-specific mortality, or disease recurrence.ConclusionOur study demonstrated that autoimmune disease does not impair the OS and DFS of HCC patients undergoing liver resections. AD itself is not a risk factor for tumor recurrence after surgery. Patients eligible for liver resections, as a result, should be considered for surgery irrespective of the presence of AD. Further studies are mandatory to validate our findings.

The prognostic significance of preoperative platelet-to-lymphocyte ratio and interleukin-6 level in non-muscle invasive bladder cancer.

Non-muscle invasive bladder cancer (NMIBC) is the most prevalent type of bladder cancer, typically associated with a favorable prognosis and a risk of recurrence during the follow-up period. Inflammatory markers have been used to predict prognosis in various cancer types. The aim of this study was to explore the prognostic value of the readily accessible inflammatory markers, platelet-to-lymphocyte ratio (PLR) and interleukin-6 (IL-6), in NMIBC. The study comprised a retrospective analysis of clinical data collected from NMIBC patients diagnosed between October 2018 and October 2020. PLR was calculated using the routine preoperative blood test results, and preoperative IL-6 levels were recorded. Receiver operating characteristic (ROC) curves were generated for PLR and IL-6 level and the optimal cut-off values were determined using Youden's index. Survival curves were generated to evaluate the association between PLR and IL-6, and recurrence-free survival (RFS), and univariate and multivariate analysis were performed using the Cox proportional hazards regression model. A nomogram and calibration curve were generated to assess the clinical significance of the model. The ROC curves demonstrated that PLR and IL-6 levels were significantly associated with tumor pathology grade, with area under the curve (AUC) values of 0.833 (95% CI 0.757, 0.910) for PLR and 0.724 (95% CI 0.622, 0.825) for IL-6 levels. PLR and IL-6 levels were also positively associated with tumor recurrence, with AUC values of 0.647 (95% CI 0.538, 0.756) and 0.846 (95% CI 0.769, 0.924), respectively. The survival curves indicated that patients with high PLR and high IL-6 levels had shorter RFS than those with low PLR and low IL-6 level (P < 0.01). Univariate Cox proportional hazards regression analysis showed that age, tumor size, tumor number, pathological grade, PLR and IL-6 were potential risk factors for NMIBC recurrence. Multivariate analysis further revealed that tumor number, smoking, PLR, and IL-6 were independent risk factors for NMIBC recurrence (P < 0.05). Preoperative peripheral blood inflammatory markers (PLR and IL-6) are useful predictors of RFS in NMIBC patients at the time of initial diagnosis. High PLR and high IL-6 were identified as independent risk factors for tumor recurrence and could serve as potential biological markers for prediction of NMIBC recurrence.

Efficacy and safety of donafenib as adjuvant therapy for patients with hepatocellular carcinoma undergoing curative resection: A retrospective, multicenter cohort study.

e16234 Background: A growing incidence of hepatocellular carcinoma and its high risk of recurrence after curative-intent treatment underscore the need for effective adjuvant treatment options. This study aimed to assess the efficacy of adjuvant donafenib in patients with hepatocellular carcinoma (HCC) following radical resection. Methods: This multicenter, real-world study retrospectively gathered clinical data of 82 patients who had undergone radical resection of HCC and received adjuvant therapy with donafenib. The primary endpoint was recurrence-free survival (RFS). The secondary endpoints included overall survival (OS) and safety. Kaplan-Meier analysis was performed to evaluate RFS and OS, while the Cox proportional-hazards model was used to estimate risk factors for tumor recurrence and death. Results: A total of 82 patients with HCC who received donafenib following surgical resection were included in the study, of which were classified as high risk for tumor recurrence (with multiple or large tumor, microvascular invasion, poor tumor differentiation). The median duration of donafenib adjuvant therapy was 10.6 months (range: 0.2–26.1 months). All patients completed follow-up as required, with a median follow-up time of 19.4 months (range: 2.8–57.6 months). During the follow-up period, a totally postoperative recurrence rate was 15.9% (13/82). 1-year recurrence rate and 2-year recurrence rate were 7.3% (6/82) and 12.2% (10/82), and 1-year survival rate and 2-year survival rate were 95.1% (78/82) and 93.9% (77/82). Kaplan-Meier analysis demonstrated that patients with higher preoperative AFP level (AFP &gt; 400ng/mL), higher preoperative PIVKA-II level (PIVKA-II &gt; 40mAU/mL), or poor tumor differentiation (Edmondson stage III-IV) exhibited higher rate of tumor recurrence after operation (all p value &lt; 0.05). Multivariate analysis indicated that preoperative AFP level was an independent risk factor for tumor recurrence in patients with donafenib treatment. Treatment-related adverse events (TRAEs) occurred in 67.1% (55/82) of patients, of which the most frequent were hand-foot syndrome (25.6%, 21/82), diarrhea (20.7%, 17/82), and fatigue (17.1%, 14/82). Only 8.5% (7/82) of patients had a grade ≥3 TRAEs, with the most common being hand-foot syndrome (2.4%, 2/82) and hypertension (2.4%, 2/82). No treatment-related deaths were reported. Conclusions: This study represents the largest multicenter investigation of adjuvant therapy with donafenib to date, and the findings indicate that donafenib has the potential to be an effective treatment option for preventing postoperative recurrence in HCC. Furthermore, the preoperative AFP ≤400ng/mL can serve as an effective biomarker for postoperative administration of donafenib in HCC patients.

Liver Resection Criteria for Patients with Hepatocellular Carcinoma and Multiple Tumors Based on Total Tumor Volume

BackgroundIn many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits.MethodsWe reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan–Meier method.ResultsIn all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria.ConclusionPatients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.

Preoperative Antiviral Therapy and Long-Term Outcomes for Hepatitis B Virus-Related Hepatocellular Carcinoma After Curative Liver Resection: A Multicenter Analysis.

To examine the association of the history of preoperative antiviral therapy (AVT) with the tumor recurrence and overall survival in HBV-related HCC patients undergoing curative-intent hepatectomy. Patients who underwent curative-intent hepatectomy for HBV-related HCC between 2014 and 2019 at 4 Chinese hospitals were analyzed. Patients were categorized as having undergone preoperative antiviral therapy (AVT) > 1 year or without antiviral therapy (non-AVT). Patient clinical features, short-term outcomes, overall survival (OS), and time-to-recurrence (TTR) were also compared. Multivariate Cox regression analysis was performed to identify the impact of preoperative AVT on the OS and TTR. Among the 565 patients, 190 (33.6%) underwent continuous AVT > 1 year before surgery. Patients in the non-AVT group were more likely to have worse liver function and more advanced tumor pathological characteristics than those in the AVT group. Postoperative morbidity and mortality rates were comparable between the two groups. Multivariate analyses revealed that a preoperative HBV viral level ≥ 2000 IU/mL was independently associated with poorer TTR (hazard ratio, 1.328; 95% CI, 1.049-1.682) and preoperative AVT was a protective factor for OS (hazard ratio, 0.691; 95% CI, 0.484-0.986). A high preoperative HBV DNA level was an independent risk factor for tumor recurrence. Preoperative AVT > 1 year was associated with better OS and a reduced incidence of tumor recurrence by inhibiting the preoperative level of HBV DNA.

Correlation of Prognostic Nutritional Index and Systemic Immune-Inflammation Index with the Recurrence and Prognosis in Oral Squamous Cell Carcinoma with the Stage of III/IV.

This study aimed to explore the correlation of systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) with the recurrence and prognosis in patients with advanced oral squamous cell carcinoma (OSCC). A total of 298 OSCC patients with the stage of III/IV were finally included in the study. SII = neutrophil count (109/L) × platelet count (109/L)/lymphocyte count (109/L). PNI = serum albumin (g/L) + 5 × total lymphocyte count (109/L). High preoperative SII and low preoperative PNI were independent risk factors for tumor recurrence in OSCC patients of the stage of III/IV. The area under the curves (AUC) for SII was 0.69 (0.63 to 0.76), for PNI was 0.72 (0.67 to 0.78), and for joint model was 0.81 (0.76 to 0.85). Patients with low level of joint model had significantly higher overall survival rate for 5 years follow-up than those with high level. Both preoperative SII and PNI are valuable independent tumor recurrence prediction index in patients with advanced OSCC. Meanwhile, the combination of preoperative SII and PNI is also valuable on OSCC recurrence and prognosis prediction.

Analysis of risk factors for postoperative recurrence of stage I colorectal cancer: a retrospective analysis of a large population.

Colorectal cancer (CRC) is the third most common cancer worldwide. Patients diagnosed with stage I CRC typically do not require postoperative adjuvant treatment. However, postoperative recurrence is present in at least 40% of patients with CRC and often occurs in those with stage I disease. This study aimed to elucidate the current status of recurrence and clinicopathological characteristics in patients with stage I CRC. Data of indicated patients were obtained from 18 registries in Surveillance, Epidemiology, and End Results (SEER). The multivariable Fine-Gray regression model was used to identify the mortality risk of patients. Disparities in survival were analyzed using Kaplan-Meier curves. Logistic regression was employed to identify factors associated with recurrent risk overestimation. Our study indicated a recurrence rate of 15.04% (1,874/12,452) in stage I CRC cases. Notably, we identified race, age, T stage, and carcinoembryonic antigen (CEA) levels as independent risk factors for tumor recurrence, substantially impacting prognosis. Furthermore, gender, race (Black), age (>65 years), elevated CEA levels, and refusal or unknown status regarding radiotherapy significantly correlated with an adverse prognosis in patients with stage I CRC. We identified certain key clinicopathological features of patients with stage I CRC and demonstrated the survival benefits of radiotherapy, offering a new perspective on stage I CRC follow-up and treatment recommendations.

"Unraveling the Tapestry": A Retrospective Exploration of Recurrent Parotid Pleomorphic Adenoma Cases.

The standard surgical procedure for treating the parotid gland's recurrent pleomorphic adenoma (RPA) is parotidectomy with facial nerve preservation (FN). Treatment of RPA remains challenging since controversies occur regarding recurrence, degree of revision surgery, postoperative radiation, and difficulty in conserving the FN. A retrospective review of patient's medical records treated for benign parotid neoplasms was conducted between 2017 and 2022 to identify individuals who underwent surgery for RPA. Demographic information, surgical intervention details, pre-and postoperative facial nerve function, histopathological analysis, and recurrence rates were collected. These variables were compared in patients with single recurrent tumors versus patients with multiple recurrent tumors. Twenty-one patients met the criteria, including 13 with a first recurrence, 7 with a second recurrence, and 1 with a third recurrence. Following surgery for multiple RPA, long-term FN outcomes were significantly worse (P = 0.005). There were no observable risk factors for tumor recurrence. The interval between the initial revision surgery and subsequent ones was drastically shortened. Our study suggests that the risk of permanent facial paralysis is greater with subsequent surgical procedures. Early detection of recurrence can aid in early re-operation.

Abstract 2695: A higher percentage of M2 macrophages in non-tumor part predict the tumor recurrence in patients with hepatocellular carcinoma after surgical resection

Abstract The primary hurdle in improving outcomes for hepatocellular carcinoma (HCC) patients after curative treatment is the high early recurrence rate. The existing literature indicates the presence of type 2 macrophages (M2), renowned for their immunosuppressive capabilities, has been implicated in creating a microenvironment conducive to tumor growth and recurrence. However, the intricate interplay involving M2 macrophages and the recurrence of HCC is underexplored. Therefore, we conducted an analysis involving HCC patients who underwent hepatectomy at our hospital between 2013 and 2017. We collected samples from both the tumor and non-tumor regions and subjected them to bulk RNA sequencing for comprehensive molecular profiling. The proportion of immune cells was calculated by CIBERSORTx.In our study, we enrolled fifty patients, with sixty percent presenting with cirrhosis and seventy-three percent having viral hepatitis. Twenty-three patients experienced tumor recurrence, with a median time to recurrence of 12.6 months. First, we found no correlation between five TIMR subtypes defined by TIMELASER (Xue R, Nature, 2022) and recurrence. However, as for the proportions of immune cell, a significantly lower NK/Treg ratio (p= 0.0163) and high within the resected tumor section in recurrent group was found. On the other hand, the ratio of M2 macrophages to total macrophages (M2/M) was significantly higher within the non-tumor region in patients experiencing tumor recurrence after hepatectomy (p=0.0357). Furthermore, the expression of the ACGT2 gene in non-tumor part, which strongly correlates with Treg function, was significantly higher (p=0.0056) in recurrent group. In addition, the innate T cells score was increased in non-tumor pat in recurrent group but with borderline significance (p=0.0628). However, in multivariable analysis, only a higher M2/M ratio within the non-tumor region (HR 3.756, p=0.0072) were identified as independent risk factors for tumor recurrence. We also found that patients with a higher M2/M ratio had a lower percentage of cirrhotic patients (p=0.0049) and less association with TIME-IA (immune activation) subtype of HCC by TIMELASER classification (p=0.0030). In conclusion, a higher M2/M ratio within the non-tumor region predict the tumor recurrence in patients with hepatocellular carcinoma. Citation Format: Po-Ting Lin, Wei-Ting Ku, Tsung-Han Wu, Cheng-Heng Wu, Chan-Keng Yang, Wei Teng, Yung-Chang Lin, Chun-Yen Lin. A higher percentage of M2 macrophages in non-tumor part predict the tumor recurrence in patients with hepatocellular carcinoma after surgical resection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2695.

Spatial intratumor heterogeneity of programmed death-ligand 1 expression predicts poor prognosis in resected non-small cell lung cancer.

We quantified the pathological spatial intratumor heterogeneity of programmed death-ligand 1 (PD-L1) expression and investigated its relevance to patient outcomes in surgically resected non-small cell lung carcinoma (NSCLC). This study enrolled 239 consecutive surgically resected NSCLC specimens of pathological stage IIA-IIIB. To characterize the spatial intratumor heterogeneity of PD-L1 expression in NSCLC tissues, we developed a mathematical model based on texture image analysis and determined the spatial heterogeneity index of PD-L1 for each tumor. The correlation between the spatial heterogeneity index of PD-L1 values and clinicopathological characteristics, including prognosis, was analyzed. Furthermore, an independent cohort of 70 cases was analyzed for model validation. Clinicopathological analysis showed correlations between high spatial heterogeneity index of PD-L1 values and histological subtype (squamous cell carcinoma; P < .001) and vascular invasion (P = .004). Survival analysis revealed that patients with high spatial heterogeneity index of PD-L1 values presented a significantly worse recurrence-free rate than those with low spatial heterogeneity index of PD-L1 values (5-year recurrence-free survival [RFS] = 26.3% vs 47.1%, P < .005). The impact of spatial heterogeneity index of PD-L1 on cancer survival rates was verified through validation in an independent cohort. Additionally, high spatial heterogeneity index of PD-L1 values were associated with tumor recurrence in squamous cell carcinoma (5-year RFS = 29.2% vs 52.8%, P < .05) and adenocarcinoma (5-year RFS = 19.6% vs 43.0%, P < .01). Moreover, we demonstrated that a high spatial heterogeneity index of PD-L1 value was an independent risk factor for tumor recurrence. We presented an image analysis model to quantify the spatial intratumor heterogeneity of protein expression in tumor tissues. This model demonstrated that the spatial intratumor heterogeneity of PD-L1 expression in surgically resected NSCLC predicts poor patient outcomes.

The Outcome of Local Excision of Rectal Adenomas with High-Grade Dysplasia by Transanal Endoscopic Microsurgery: A Single-Center Experience.

Background: Local excision by transanal endoscopic microsurgery (TEM) is considered an acceptable treatment for rectal adenomas with high-grade dysplasia (HGD). This study aims to assess the likelihood of harboring an invasive carcinoma in preoperatively diagnosed HGD polyps and evaluate the risk factors for tumor recurrence in patients with final HGD pathology. Methods: Data from patients who underwent TEM procedures for adenomatous lesions with HGD from 2005 to 2018 at the Rabin Medical Center, Hasharon Hospital, were analyzed. Collected data included patient demographics, preoperative workup, tumor characteristics and postoperative results. Follow-up data including recurrence assessment and further treatments were reviewed. The analysis included two subsets: preoperative pathology of HGD (sub-group 1) and postoperative final pathology of HGD (sub-group 2) patients. Results: Forty-five patients were included in the study. Thirty-six patients had a preoperative diagnosis of HGD, with thirteen (36%) showing postoperative invasive carcinoma. Thirty-two patients had a final pathology of HGD, and three (9.4%) experienced tumor recurrence. Large tumor size (>5 cm) was significantly associated with recurrence (p = 0.03). Conclusions: HGD rectal polyps are associated with a significant risk of invasive cancer. Tumor size was a significant factor in predicting tumor recurrence in patients with postoperative HGD pathology. The TEM procedure is an effective first-line treatment for such lesions.

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

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

Clinical Outcome after Surgical Treatment of Sacral Chordomas: A Single-Center Retrospective Cohort of 27 Patients.

Introduction: The aims of our study were (1) to determine disease-specific and disease-free survival after the en-bloc resection of sacral chordomas and (2) to investigate potential risk factors for tumor recurrence and major postoperative wound-related complications. Methods: We retrospectively analyzed 27 consecutive patients with sacral chordomas who were surgically treated in our institution between 2004 and 2022. Three patients (11.1%) had a recurrent tumor and four patients (14.8%) had history of a second primary solid tumor prior to or after their sacral chordoma. A combined anterior and posterior approach, colostomy, plastic reconstruction, and spinopelvic instrumentation were necessitated in 51.9%, 29.6%, 37%, and 7.4% of cases, respectively. The mean duration of follow-up was 58 ± 41 months (range= 12-170). Death-related-to-disease, disease recurrence, and major surgical site complications were analyzed using Kaplan-Meier survival analysis, and investigation of the respective risk factors was performed with Cox hazard regression. Results: The estimated 5-year and 10-year disease-specific survival was 75.3% (95% CI = 49.1-87.5%) and 52.7% (95% CI = 31-73.8%), respectively. The estimated 1-year, 5-year, and 10-year disease-free survival regarding local and distant disease recurrence was 80.4% (95% CI = 60.9-91.1%), 53.9% (95% CI = 24.6-66.3%), and 38.5% (95% CI = 16.3-56.2%), respectively. The mean survival of the recurred patients was 61.7 ± 33.4 months after their tumor resection surgery. Conclusions: Despite the high relapse rates and perioperative morbidity, long-term patient survival is not severely impaired. Positive or less than 2 mm negative resection margins have a significant association with disease progression.

Liver Transplantation for Hepatocellular Carcinoma beyond the Milan Criteria: A Specific Role for Living Donor Liver Transplantation after Neoadjuvant Therapy.

This study was designed to elucidate the various new classifications and the use of LDLT and bridging therapy for HCC in this context beyond the Milan criteria (MC). The clinical data of patients with HCC outside the MC who underwent LT at Jena University between January 2007 and August 2023 were retrospectively analysed. Eligible patients were classified according to various classification systems. Clinicopathological features, overall and disease-free survival rates were compared between LT and LDLT within the context of bridging therapy. Among the 245 patients analysed, 120 patients did not meet the MC, and 125 patients met the MC. Moreover, there were comparable overall survival rates between patients outside the MC for LT versus LDLT (OS 44.3 months vs. 28.3 months; 5-year survival, 56.4% vs. 40%; p = 0.84). G3 tumour differentiation, the presence of angioinvasion and lack of bridging were statistically significant risk factors for tumour recurrence according to univariate and multivariate analyses (HR 6.34; p = 0.0002; HR 8.21; p < 0.0001; HR 7.50; p = 0.0001). Bridging therapy before transplantation provided a significant survival advantage regardless of the transplant procedure (OS: p = 0.008; DFS: p < 0.001). Patients with HCC outside the MC who underwent LT or LDLT had worse outcomes compared to those of patients who met the MC but still had a survival advantage compared to patients without transplantation. Nevertheless, such patients remain disadvantaged on the waiting list, which is why LDLT represents a safe alternative to LT and should be considered in bridged HCC patients because of differences in tumour differentiation, size and tumour marker dynamics.

Evaluation of the efficacy of transarterial chemoembolization combined with microwave ablation followed by adjuvant therapy in patients with hepatocellular carcinoma.

This study aimed to explore the efficacy of transarterial chemoembolization (TACE) combined with microwave ablation (MWA) adjuvant to lenvatinib and anti-PD-1 antibodies for patients with hepatocellular carcinoma (HCC). A retrospective analysis of 67 patients with HCC treated at our hospital between October 2018 and May 2022 was conducted. All patients underwent a combination of TACE and MWA. Among them, 29 received postoperative treatment with molecular-targeted agents, like lenvatinib, along with anti-PD-1 antibodies such as sindilizumab, karelizumab, or tirilizumab. The remaining 38 patients did not receive postoperative systemic therapies, like targeted or immunotherapy. The survival and prognosis of all patients were analyzed. Nine patients in the observation group and 29 patients in the control group experienced recurrence, and the median progression-free survival 1 (PFS1) was not reached 'Not Applicable'(NA) and 17.05 months (P=0.035), respectively. Failure to combine adjuvant therapy was identified as an independent risk factor for tumor recurrence, and the observation group had a 0.245 times lower risk of recurrence compared to that in the control group (P=0.005). Multivariable Cox regression analysis confirmed that the maximum tumor size, and tumor number were risk factors for tumor recurrence. Patients with a large maximum tumor size had a 1.519 times higher risk of recurrence compared to those with a small maximum tumor size (P=0.006), and patients with a large number of tumors had a 5.978 times higher risk of recurrence compared to those with a small number of tumors (P=0.02). The median PFS2 of the two groups was 11.795 and 21.257 months, respectively, though not statistically significant (P=0.955). However, there was a disparity in the percentage of BCLC stages associated with recurrence between the two groups. In the observation group approximately 22.22% of patients progressed to stage C, while in the control group, this proportion was 34.48%. The observation group exhibited a lower risk of distant metastasis compared to the control group. Adjuvant treatment of HCC following TACE combined with MWA improved PFS and achieved better clinical outcomes compared to that with TACE combined with MWA alone.

Noninvasive prediction of perineural invasion in intrahepatic cholangiocarcinoma by clinicoradiological features and computed tomography radiomics based on interpretable machine learning: a multicenter cohort study.

Perineural invasion (PNI) of intrahepatic cholangiocarcinoma (ICC) is a strong independent risk factor for tumour recurrence and long-term patient survival. However, there is a lack of noninvasive tools for accurately predicting the PNI status. The authors develop and validate a combined model incorporating radiomics signature and clinicoradiological features based on machine learning for predicting PNI in ICC, and used the Shapley Additive explanation (SHAP) to visualize the prediction process for clinical application. This retrospective and prospective study included 243 patients with pathologically diagnosed ICC (training, n =136; external validation, n =81; prospective, n =26, respectively) who underwent preoperative contrast-enhanced computed tomography between January 2012 and May 2023 at three institutions (three tertiary referral centres in Guangdong Province, China). The ElasticNet was applied to select radiomics features and construct signature derived from computed tomography images, and univariate and multivariate analyses by logistic regression were used to identify the significant clinical and radiological variables with PNI. A robust combined model incorporating radiomics signature and clinicoradiological features based on machine learning was developed and the SHAP was used to visualize the prediction process. A Kaplan-Meier survival analysis was performed to compare prognostic differences between PNI-positive and PNI-negative groups and was conducted to explore the prognostic information of the combined model. Among 243 patients (mean age, 61.2years ± 11.0 (SD); 152 men and 91 women), 108 (44.4%) were diagnosed as PNI-positive. The radiomics signature was constructed by seven radiomics features, with areas under the curves of 0.792, 0.748, and 0.729 in the training, external validation, and prospective cohorts, respectively. Three significant clinicoradiological features were selected and combined with radiomics signature to construct a combined model using machine learning. The eXtreme Gradient Boosting exhibited improved accuracy and robustness (areas under the curves of 0.884, 0.831, and 0.831, respectively). Survival analysis showed the construction combined model could be used to stratify relapse-free survival (hazard ratio, 1.933; 95% CI: 1.093-3.418; P =0.021). We developed and validated a robust combined model incorporating radiomics signature and clinicoradiological features based on machine learning to accurately identify the PNI statuses of ICC, and visualize the prediction process through SHAP for clinical application.