1.Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions
Suqin YANG ; Sunbin LING ; Jianhua LI ; Yan WANG ; Jiapei WANG ; Qiwei HUANG ; Fanming LIU ; Yiqi ZHUANG ; Yingyu ZHENG ; Rui WANG ; Zhe YANG ; Xiaoping ZHENG ; Kai WANG ; Zhikun LIU ; Jun CHEN ; Jianguo WANG ; Haiyang XIE ; Lin ZHOU ; Leiming CHEN ; Guoqiang CAO ; Dandan CHEN ; Junfang JI ; Bin ZHAO ; Chao JIANG ; Di LU ; Xuyong WEI ; Hangjin JIANG ; Qiaonan SHAN ; Hengbo SHI ; Yong-Zhen XU ; Shusen ZHENG ; Zhengxin WANG ; Shengda LIN ; Xiao XU
Clinical and Molecular Hepatology 2026;32(2):884-903
Background/Aims:
Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods:
We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results:
We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion
Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.
2.Trends of Incidence and Age at Onset of Bone Malignant Tumors in Jiangsu Cancer Registration Areas from 2009 to 2019
Pei ZHAO ; Ye XIE ; Qiumei LI ; Qiwei WANG ; Renqiang HAN ; Weigang MIAO ; Ran TAO ; Jinyi ZHOU
China Cancer 2025;34(8):618-625
[Purpose]To analyze the trends of incidence and age at onset of bone malignant tumors in cancer registration areas of Jiangsu Province from 2009 to 2019.[Methods]Incidence data of bone malignant tumors from 2009 to 2019 were collected from 16 consecutive and quality-con-trolled cancer registries in Jiangsu Province.The incidence rates,average age at onset,and inci-dence composition of bone malignant tumors were calculated.A birth cohort model was constructed to analyze the changes in the incidence of bone malignant tumors in the population born from 1929 to 2019.Joinpoint regression models were used to analyze the average annual percentage change(AAPC)in the incidence rates and the incidence composition of bone malignant tumors for each year in those aged 60 years old and above.A general linear regression model was used to ana-lyze the trend of the average age of onset.[Results]The crude incidence rate of bone malignant tumors in women in Jiangsu cancer registration areas decreased from 2009 to 2019,with an AAPC of-2.62%(P=0.025).After adjusting the population composition,except for urban areas,the incidence of bone malignant tumors in the whole province,men,women and rural areas all decreased significantly,with AAPC of-3.15%,-2.49%,-4.31%and-2.23%,respectively.The average age at onset of bone malignant tumors in the whole province,men and urban areas de-creased significantly yearly,with an average annual decrease of 0.365,0.504 and 0.469 years old,respectively.In the same period,the incidence of malignant bone tumors in the whole province,men,women and urban areas of age groups of 50~59,60~69 and 70~79 years old showed a decreasing trend,the AAPC ranged from-9.06%to-4.14%(all P<0.05),and the inci-dence decreased gradually with the year of birth.The incidence of malignant bone tumors in men<30 years old increased yearly with an AAPC of 4.30%(P<0.05).Compared with 2009,the com-position of incidence in men aged 15~39 years old and in urban population increased in 2019,while the incidence of bone malignant tumors in the age group of 60~79 years old in the province generally decreased.After age structure adjustment,the incidence of bone malignant tumors in people over 60 years old in urban areas decreased with an AAPC of-1.42%(P<0.05).[Conclu-sion]The incidence of bone malignant tumors in Jiangsu Province is decreasing and the age at on-set is moving forward,indicating that the prevention and control measures of bone malignant tu-mors should be adjusted accordingly.
3.Clinical application study of the "two-winged" retraction technique in laparoscopic complete mesocolic resection for the left hemicolon
Lifeng XIE ; Jing JIA ; Qiwei CHEN ; Jianbin HOU ; Yan LIU ; Yiyang WU ; Xinyu LI
Chinese Journal of Gastrointestinal Surgery 2025;28(4):412-416
Objective:To explore the application value of the "Dual-Wing" traction technique in the medial & head lateral laparoscopic left hemicolectomy with radical resection.Methods:The "Dual-Wing " traction technique is based on the theory of mesenteric anatomy. The assistant lifts the proper mesentery of the digestive tract to be resected or the adjacent mesenteric tissue connected to it,thereby elevating the target organ and its mesentery as a whole away from the mesenteric bed. By utilizing the tension transmission between the proper mesenteries of adjacent organs to create counter-tension,the surgeon's operative actions are always maintained along the line of maximum counter-tension.After incising the mesenteric fusion line,this technique assists the surgeon in entering the fusion plane. A descriptive case series study method was adopted to retrospectively analyze the clinical and pathological data of 37 colorectal cancer patients who underwent laparoscopic left hemicolectomy with the "Dual-Wing" traction technique via a medial and cephalad approach, performed by the Department of Gastrointestinal Surgery at Dongjie Campus of the First Hospital of Quanzhou, Fujian Medical University, from May 2023 to November 2023.Results:All patients successfully underwent laparoscopic left hemicolectomy via the medial & head lateral approach using the "Dual-Wing" traction technique.The surgery adhered to the principles of total mesocolic excision and safely mobilized the left colon and its mesentery from the correct anatomical plane. In the entire group of patients,there were 14 males and 23 females; the mean operative time was 94.1±18.3 minutes; the mean intraoperative blood loss was 9.8±5.4 ml; the mean number of lymph nodes dissected was 18.1±3.9; the mean number of positive lymph nodes was 1.4±1.6; the pathological specimen resection margin grading was Grade A in 29 cases, Grade B in 8 cases, and no Grade C cases; the tumor TNM staging was Stage I in 3 cases, Stage IIA in 7 cases, Stage IIB in 6 cases, Stage IIIA in 2 cases, Stage IIIB in 15 cases, and Stage IIIC in 4 cases; the mean time to first flatus postoperatively was 35.7±7.5 hours; the mean length of hospital stay was 9.1±1.7 days. There were no intraoperative injuries to the pancreas or spleen. Postoperative complications occurred in 3 cases. No anastomotic leakage was observed in the entire group, and there were no deaths following the surgery.Conclusion:The application of the "Dual-Wing" traction technique to establish a stable surgical scenario can significantly reduce the demands on the assistant. It is conducive to maintaining mesenteric tension and fully exposing the surgical field. It also allows for the rapid identification and maintenance of the correct anatomical plane. For colorectal cancer patients, the surgery is safe and feasible, with satisfactory short-term therapeutic effects.
4.Effect of side-to-end anastomosis on postoperative bowel function in rectal cancer surgery: a prospective single-center randomized controlled trial
Chang WANG ; Fan LIU ; Sen HOU ; Zhanlong SHEN ; Mujun YIN ; Xiaodong YANG ; Kewei JIANG ; Qiwei XIE ; Bin LIANG ; Kai SHEN ; Zhidong GAO ; Yingjiang YE
Chinese Journal of Gastrointestinal Surgery 2025;28(6):644-652
Objective:To compare bowel function 12 months after surgery between side-to-end anastomosis (SEA) and end-to-end anastomosis (EEA) groups of patients who had undergone rectal cancer resection.Methods:This single-center, prospective, open-label, phase III randomized controlled trial was approved by the Ethics Committee of Peking University People's Hospital (2018PHB040-01) and registered at ClinicalTrials. org (NCT03669237). Inclusion criteria were as follows: (1) histologically confirmed rectal adenocarcinoma; (2) tumor located 0 to 12 cm from the anal verge; (3) age≥18 years; and (4) planned R0 resection with primary reconstruction. Exclusion criteria included: (1) emergency surgery; (2) cognitive impairment; (3) non-primary anastomosis; (4) history of left-sided colonic or anorectal surgery; and (5) preexisting chronic defecation dysfunction. Eligible rectal cancer patients scheduled for elective sphincter-preserving surgery at Peking University People's Hospital were prospectively enrolled between October 2018 and March 2021 and randomly assigned to either the EEA group or the SEA group via computer-generated numbers prior to entering the operating room. All patients underwent standard radical tumor resection. Bowel function was evaluated by the low anterior resection syndrome (LARS) questionnaire. It consists of five single-choice questions and yields a total score ranging from 0 to 42. Defecation function is categorized into three levels: no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30-42 points). The primary endpoint was the LARS score 12 months after surgery. Secondary endpoints included LARS scores from 1 to 11 months and during long-term follow-up(>12 months). The final follow-up was completed in July 2022. All randomized patients were included in the intention-to-treat set (ITTS). The full analysis set (FAS) was defined as ITTS patients with valid outcome data. All primary statistical analyses were performed in the FAS, and results were further compared in the per-protocol set (PPS) based on the actual treatment received.Results:A total of 323 patients underwent eligibility assessment, of whom 71 did not meet the inclusion criteria and 52 declined to participate. Ultimately, 200 patients were randomized. Median age was 64 years and 85 were women. The SEA and EEA groups comprised 102 and 98 patients, respectively. A total of 181 patients (90.5%) were included in the FAS, and 170 (85.0%) were included in the PPS. Among these, the 12-month LARS score was evaluated in 178 patients (98.3%) in the FAS and in 167 (98.2%) in the PPS. Median LARS score at 1–12 months were significantly lower in the SEA group in both the FAS dataset [12 months:8 (interquartile range [IQR], 0–22) vs. 14 (IQR, 8–29); Z=2.687, P=0.007] and the PPS dataset [12 months: 8 (IQR, 0–22) vs. 14 (IQR, 6–29); Z=2.543, P=0.011]. During long-term follow-up, the median LARS score was also significantly lower in the SEA group in the FAS dataset [2 (IQR, 0–4) vs. 11 (IQR, 2–23); Z=2.968, P=0.003] and the PPS dataset [2 (IQR, 0–14) vs. 11 (2, 27); Z=2.687, P=0.007]. Conclusion:Compared with the EEA group, bowel function was superior in the SEA group 1 year after surgery and during long-term follow-up.
5.Implementation efficacy of Guangxi's"regulations on medical dispute prevention and resolution"from healthcare practitioners' perspective
Ziyi YE ; Lu YE ; Qiwei LI ; Qingsong XIE ; Mengqing LIU
Modern Hospital 2025;25(5):669-672,678
Objective To assess the effectiveness of the Regulations on Medical Dispute Prevention and Resolution(hereafter referred to as the Regulations)and to provide evidence-based recommendations for enhancing the legal governance sys-tem of medical dispute management.Methods A cross-sectional study was conducted involving physicians,nurses,techni-cians,clinical department directors,and head nurses.The investigation was conducted through literature review,questionnaire surveys,and expert interviews.Factor analysis and chi-square tests were employed for statistical analysis.Results Significant differences(P<0.01)were observed among healthcare practitioners in Guangxi concerning their understanding of the Regula-tions,preferences for dispute resolution methods,implementation of informed consent,and risk intervention practices.However,no significant differences emerged in medical quality and safety evaluations or recommendations for surgical accident insurance.Conclusion This study suggests it is a need to refine the legal framework for medical dispute prevention and resolution.It is rec-ommended to strengthen medical personnel's compliance with informed consent obligations and deepen their understanding of rel-evant laws and regulations.Efforts should be intensified to promote third-party mediation mechanisms such as the Medical Dispute Mediation Committee(MedMC)and medical accident insurance coverage.Additionally,pre-dispute risk assessments should be enhanced,and a risk early intervention model integrating artificial intelligence,healthcare practices,and legal regulations should be established.
6.Implementation efficacy of Guangxi's"regulations on medical dispute prevention and resolution"from healthcare practitioners' perspective
Ziyi YE ; Lu YE ; Qiwei LI ; Qingsong XIE ; Mengqing LIU
Modern Hospital 2025;25(5):669-672,678
Objective To assess the effectiveness of the Regulations on Medical Dispute Prevention and Resolution(hereafter referred to as the Regulations)and to provide evidence-based recommendations for enhancing the legal governance sys-tem of medical dispute management.Methods A cross-sectional study was conducted involving physicians,nurses,techni-cians,clinical department directors,and head nurses.The investigation was conducted through literature review,questionnaire surveys,and expert interviews.Factor analysis and chi-square tests were employed for statistical analysis.Results Significant differences(P<0.01)were observed among healthcare practitioners in Guangxi concerning their understanding of the Regula-tions,preferences for dispute resolution methods,implementation of informed consent,and risk intervention practices.However,no significant differences emerged in medical quality and safety evaluations or recommendations for surgical accident insurance.Conclusion This study suggests it is a need to refine the legal framework for medical dispute prevention and resolution.It is rec-ommended to strengthen medical personnel's compliance with informed consent obligations and deepen their understanding of rel-evant laws and regulations.Efforts should be intensified to promote third-party mediation mechanisms such as the Medical Dispute Mediation Committee(MedMC)and medical accident insurance coverage.Additionally,pre-dispute risk assessments should be enhanced,and a risk early intervention model integrating artificial intelligence,healthcare practices,and legal regulations should be established.
7.Clinical application study of the "two-winged" retraction technique in laparoscopic complete mesocolic resection for the left hemicolon
Lifeng XIE ; Jing JIA ; Qiwei CHEN ; Jianbin HOU ; Yan LIU ; Yiyang WU ; Xinyu LI
Chinese Journal of Gastrointestinal Surgery 2025;28(4):412-416
Objective:To explore the application value of the "Dual-Wing" traction technique in the medial & head lateral laparoscopic left hemicolectomy with radical resection.Methods:The "Dual-Wing " traction technique is based on the theory of mesenteric anatomy. The assistant lifts the proper mesentery of the digestive tract to be resected or the adjacent mesenteric tissue connected to it,thereby elevating the target organ and its mesentery as a whole away from the mesenteric bed. By utilizing the tension transmission between the proper mesenteries of adjacent organs to create counter-tension,the surgeon's operative actions are always maintained along the line of maximum counter-tension.After incising the mesenteric fusion line,this technique assists the surgeon in entering the fusion plane. A descriptive case series study method was adopted to retrospectively analyze the clinical and pathological data of 37 colorectal cancer patients who underwent laparoscopic left hemicolectomy with the "Dual-Wing" traction technique via a medial and cephalad approach, performed by the Department of Gastrointestinal Surgery at Dongjie Campus of the First Hospital of Quanzhou, Fujian Medical University, from May 2023 to November 2023.Results:All patients successfully underwent laparoscopic left hemicolectomy via the medial & head lateral approach using the "Dual-Wing" traction technique.The surgery adhered to the principles of total mesocolic excision and safely mobilized the left colon and its mesentery from the correct anatomical plane. In the entire group of patients,there were 14 males and 23 females; the mean operative time was 94.1±18.3 minutes; the mean intraoperative blood loss was 9.8±5.4 ml; the mean number of lymph nodes dissected was 18.1±3.9; the mean number of positive lymph nodes was 1.4±1.6; the pathological specimen resection margin grading was Grade A in 29 cases, Grade B in 8 cases, and no Grade C cases; the tumor TNM staging was Stage I in 3 cases, Stage IIA in 7 cases, Stage IIB in 6 cases, Stage IIIA in 2 cases, Stage IIIB in 15 cases, and Stage IIIC in 4 cases; the mean time to first flatus postoperatively was 35.7±7.5 hours; the mean length of hospital stay was 9.1±1.7 days. There were no intraoperative injuries to the pancreas or spleen. Postoperative complications occurred in 3 cases. No anastomotic leakage was observed in the entire group, and there were no deaths following the surgery.Conclusion:The application of the "Dual-Wing" traction technique to establish a stable surgical scenario can significantly reduce the demands on the assistant. It is conducive to maintaining mesenteric tension and fully exposing the surgical field. It also allows for the rapid identification and maintenance of the correct anatomical plane. For colorectal cancer patients, the surgery is safe and feasible, with satisfactory short-term therapeutic effects.
8.Effect of side-to-end anastomosis on postoperative bowel function in rectal cancer surgery: a prospective single-center randomized controlled trial
Chang WANG ; Fan LIU ; Sen HOU ; Zhanlong SHEN ; Mujun YIN ; Xiaodong YANG ; Kewei JIANG ; Qiwei XIE ; Bin LIANG ; Kai SHEN ; Zhidong GAO ; Yingjiang YE
Chinese Journal of Gastrointestinal Surgery 2025;28(6):644-652
Objective:To compare bowel function 12 months after surgery between side-to-end anastomosis (SEA) and end-to-end anastomosis (EEA) groups of patients who had undergone rectal cancer resection.Methods:This single-center, prospective, open-label, phase III randomized controlled trial was approved by the Ethics Committee of Peking University People's Hospital (2018PHB040-01) and registered at ClinicalTrials. org (NCT03669237). Inclusion criteria were as follows: (1) histologically confirmed rectal adenocarcinoma; (2) tumor located 0 to 12 cm from the anal verge; (3) age≥18 years; and (4) planned R0 resection with primary reconstruction. Exclusion criteria included: (1) emergency surgery; (2) cognitive impairment; (3) non-primary anastomosis; (4) history of left-sided colonic or anorectal surgery; and (5) preexisting chronic defecation dysfunction. Eligible rectal cancer patients scheduled for elective sphincter-preserving surgery at Peking University People's Hospital were prospectively enrolled between October 2018 and March 2021 and randomly assigned to either the EEA group or the SEA group via computer-generated numbers prior to entering the operating room. All patients underwent standard radical tumor resection. Bowel function was evaluated by the low anterior resection syndrome (LARS) questionnaire. It consists of five single-choice questions and yields a total score ranging from 0 to 42. Defecation function is categorized into three levels: no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30-42 points). The primary endpoint was the LARS score 12 months after surgery. Secondary endpoints included LARS scores from 1 to 11 months and during long-term follow-up(>12 months). The final follow-up was completed in July 2022. All randomized patients were included in the intention-to-treat set (ITTS). The full analysis set (FAS) was defined as ITTS patients with valid outcome data. All primary statistical analyses were performed in the FAS, and results were further compared in the per-protocol set (PPS) based on the actual treatment received.Results:A total of 323 patients underwent eligibility assessment, of whom 71 did not meet the inclusion criteria and 52 declined to participate. Ultimately, 200 patients were randomized. Median age was 64 years and 85 were women. The SEA and EEA groups comprised 102 and 98 patients, respectively. A total of 181 patients (90.5%) were included in the FAS, and 170 (85.0%) were included in the PPS. Among these, the 12-month LARS score was evaluated in 178 patients (98.3%) in the FAS and in 167 (98.2%) in the PPS. Median LARS score at 1–12 months were significantly lower in the SEA group in both the FAS dataset [12 months:8 (interquartile range [IQR], 0–22) vs. 14 (IQR, 8–29); Z=2.687, P=0.007] and the PPS dataset [12 months: 8 (IQR, 0–22) vs. 14 (IQR, 6–29); Z=2.543, P=0.011]. During long-term follow-up, the median LARS score was also significantly lower in the SEA group in the FAS dataset [2 (IQR, 0–4) vs. 11 (IQR, 2–23); Z=2.968, P=0.003] and the PPS dataset [2 (IQR, 0–14) vs. 11 (2, 27); Z=2.687, P=0.007]. Conclusion:Compared with the EEA group, bowel function was superior in the SEA group 1 year after surgery and during long-term follow-up.
9.Trends of Incidence and Age at Onset of Bone Malignant Tumors in Jiangsu Cancer Registration Areas from 2009 to 2019
Pei ZHAO ; Ye XIE ; Qiumei LI ; Qiwei WANG ; Renqiang HAN ; Weigang MIAO ; Ran TAO ; Jinyi ZHOU
China Cancer 2025;34(8):618-625
[Purpose]To analyze the trends of incidence and age at onset of bone malignant tumors in cancer registration areas of Jiangsu Province from 2009 to 2019.[Methods]Incidence data of bone malignant tumors from 2009 to 2019 were collected from 16 consecutive and quality-con-trolled cancer registries in Jiangsu Province.The incidence rates,average age at onset,and inci-dence composition of bone malignant tumors were calculated.A birth cohort model was constructed to analyze the changes in the incidence of bone malignant tumors in the population born from 1929 to 2019.Joinpoint regression models were used to analyze the average annual percentage change(AAPC)in the incidence rates and the incidence composition of bone malignant tumors for each year in those aged 60 years old and above.A general linear regression model was used to ana-lyze the trend of the average age of onset.[Results]The crude incidence rate of bone malignant tumors in women in Jiangsu cancer registration areas decreased from 2009 to 2019,with an AAPC of-2.62%(P=0.025).After adjusting the population composition,except for urban areas,the incidence of bone malignant tumors in the whole province,men,women and rural areas all decreased significantly,with AAPC of-3.15%,-2.49%,-4.31%and-2.23%,respectively.The average age at onset of bone malignant tumors in the whole province,men and urban areas de-creased significantly yearly,with an average annual decrease of 0.365,0.504 and 0.469 years old,respectively.In the same period,the incidence of malignant bone tumors in the whole province,men,women and urban areas of age groups of 50~59,60~69 and 70~79 years old showed a decreasing trend,the AAPC ranged from-9.06%to-4.14%(all P<0.05),and the inci-dence decreased gradually with the year of birth.The incidence of malignant bone tumors in men<30 years old increased yearly with an AAPC of 4.30%(P<0.05).Compared with 2009,the com-position of incidence in men aged 15~39 years old and in urban population increased in 2019,while the incidence of bone malignant tumors in the age group of 60~79 years old in the province generally decreased.After age structure adjustment,the incidence of bone malignant tumors in people over 60 years old in urban areas decreased with an AAPC of-1.42%(P<0.05).[Conclu-sion]The incidence of bone malignant tumors in Jiangsu Province is decreasing and the age at on-set is moving forward,indicating that the prevention and control measures of bone malignant tu-mors should be adjusted accordingly.
10.Tumor deposit is an independent prognostic factor in patients with gastric cancer after radical gastrectomy
Liquan ZHOU ; Yushi ZHOU ; Qiwei XIE ; Yingjiang YE ; Bin LIANG
Chinese Journal of General Surgery 2024;39(10):790-796
Objective:To investigate the effect of tumor deposit(TD) on the prognosis of patients with gastric cancer after radical surgery.Methods:A retrospective analysis was performed on gastric cancer patients who underwent radical surgery at the Department of Gastrointestinal Surgery, Peking University People's Hospital from Jan 2021 to Dec 2023. The relationship between the status of tumor deposit and clinicopathological features, as well as the impact on the overall postoperative survival of gastric cancer patients were evaluated.Results:Pathological examination revealed that among 212 patients with gastric cancer, 12 patients (5.1%) had tumor deposits (TD). The occurrence of TD was found to be associated with preoperative T stage, N stage, and extramural vascular invasion (EMVI) (all P<0.05). During the follow-up period, 31 patients experienced recurrence, metastasis, or death. The COX multivariate analysis indicated that N stage ( P=0.07), preoperative serum CEA level ( P<0.001), EMVI ( P=0.001), and TD ( P=0.011) were independent risk factors affecting the overall postoperative survival . Among patients who received neoadjuvant therapy and on pT4 stage, pN+ status, and EMVI status before surgery, the presence of TD was closely correlated with overall survival. Patients with TD had a worse prognosis and shorter overall survival( P<0.05). Conclusion:Tumor deposit is an important risk factor affecting the prognosis of patients after radical gastrectomy and may be a predictive biomarker of early peritoneal metastasis.

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