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Colorectal cancer (CRC) is a highly prevalent malignancy affecting the digestive system on a global scale. This study aimed to explore the previously unexplored role of CHPF in the progression of CRC. Our results revealed a significant upregulation of CHPF expression in CRC tumour tissues compared to normal tissues, with its levels correlating with tumour malignancy. In vitro experiments using CRC cell lines demonstrated that inhibiting CHPF expression suppressed cell proliferation, colony formation and cell migration, while promoting apoptosis. Conversely, overexpressing CHPF had the opposite effect. Additionally, our xenograft models in mice confirmed the inhibitory impact of CHPF knockdown on CRC progression using various cell models. Mechanistic investigations unveiled that CHPF may enhance VEGFB expression through E2F1-mediated transcription. Functionally, suppressing VEGFB expression successfully mitigated the oncogenic effects induced by CHPF overexpression. Collectively, these findings suggest that CHPF may act as a tumour promoter in CRC, operating in a VEGFB-dependent manner and could be a potential target for therapeutic interventions in CRC treatment.
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Apoptosis , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Factor B de Crecimiento Endotelial Vascular , Anciano , Animales , Femenino , Humanos , Masculino , Ratones , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Ratones Desnudos , Transcripción Genética , Factor B de Crecimiento Endotelial Vascular/metabolismo , Factor B de Crecimiento Endotelial Vascular/genéticaRESUMEN
Background: Overall survival (OS) varies significantly among individuals with heterogeneous retroperitoneal liposarcoma (RPLS), even among those with the same clinical stage. Improved staging of RPLS is a critical unmet need, given the disappointing results of external validations of the 8th American Joint Committee on Cancer (AJCC) TNM staging system. Methods: The cohort study included 220 consecutive patients who underwent surgical resection for primary RPLS at the largest sarcoma centre of Fudan University in China from September 2009 to August 2021, combined with 277 adult patients with RPLS in the SEER database from 1975 to 2020. Data analysis was performed from December 2021 to December 2022. Patients were retrospectively restaged according to the 8th and 7th editions of the TNM staging system as well as the new TNM (nTNM) staging system. The primary endpoint was overall survival (OS). Comparative analysis of postoperative survival was performed using the Kaplan-Meier method, and differences between subgroups were tested using the log-rank test. The OS prediction nomogram was generated based on baseline variables and tumour characteristics. Harrell's consistency index (C-index), area under the curve (AUC) of receiver operating characteristic curves (ROC), and calibration curves were used to evaluate the performance of the nomogram. Results: A total of 497 patients were enrolled in the study, including 282 (56.7%) male patients. The median follow-up was 51 months (interquartile range, IQR, 23-83), and the OS rates at 1, 3, and 5 years were 87.9%, 75.3%, and 64.9%, respectively. According to the staging distribution of the AJCC 7th edition, 6 patients were stage IA (1.2%), 189 patients were stage IB (38%), 12 patients were stage IIA (2.4%), 150 patients were stage IIB (30.1%), 131 patients were stage III (26.3%), and 9 patients were stage IV (1.8%). With the 8th edition staging, this distribution changed: 6 patients (1.2%) were stage IA, 189 patients (38%) were stage IB, 12 patients (2.4%) were stage II, 24 patients (4.8%) were stage IIIA, 257 patients (51.7%) were stage IIIB, and 9 patients (1.8%) were stage IV. 182 patients (36.6%) were reclassified according to the nTNM staging system with the new T stage classification. The C-index and log-rank score improved after implementation of nTNM implementation. The nTNM system was associated with improved identification of high-risk patients compared with the AJCC 7th and 8th TNM. The FNCLCC stage proved to be highly prognostic with significant intergroup differences in OS. The calibration curve shows a high degree of agreement between the actual OS rate and the nomogram estimated OS rate. Conclusion: Compared with 8th AJCC TNM, 7th AJCC TNM staging system showed a more homogeneous staging distribution and a slight improvement in the prognostic accuracy of RPLS. The revised T-stage and nTNM systems showed better risk stratification performance. The FNCLCC stage was found to have high prognostic value, further emphasising histological grade is the least negligible prognostic factor in predicting patient survival. The constructed nomogram model enables individualized prognostic analysis and helps to develop risk-adapted therapy for RPLS patients.
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BACKGROUND: To assess the correlation between clinical outcomes and diagnostic accuracy of evaluations carried out by a preoperative multidisciplinary team versus standard surgical care for patients with retroperitoneal liposarcoma undergoing surgery. METHODS: This comparative study was conducted retrospectively at a specialist assessment center within Zhongshan Hospital, Fudan University, China, between April 2011 and March 2021. Patients were assigned to a multidisciplinary team or nonmultidisciplinary team cohort based on referral to the multidisciplinary team. The primary outcome measured was long-term clinical prognosis, with other outcomes including diagnostic accuracy, 30-day reoperation, duration of stay, perioperative mortality, and medical complications. To mitigate selection bias, we conducted propensity-score matching. Uni- and multivariable Cox proportional hazard models were then used to evaluate the effect of multidisciplinary teams on postoperative survival. The previously specified questionnaire was used to measure the enhancement of awareness and treatment adherence facilitated by multidisciplinary team management. Data analysis was carried out between January 2023 and August 2023. RESULTS: Of the 521 records that were screened, 139 patients were deemed eligible for inclusion and defined as the multidisciplinary team cohort. At the same time, 382 patients without multidisciplinary team management were also included during that period and defined as the nonmultidisciplinary team cohort. The multidisciplinary team cohort exhibited lower numbers of primary retroperitoneal liposarcoma but a higher tumor grade and a greater proportion of R2 resection. After propensity-score matching, the 1-, 3-, and 5-year overall survival rates were 89.5%, 70.5%, and 62.9%, respectively, in the multidisciplinary team cohort, and 77.1%, 49.8%, and 45.1% in the nonmultidisciplinary team cohort. The diagnostic consistency of the multidisciplinary team group was significantly superior to that of the nonmultidisciplinary cohort (92.5% vs 83.6%, P = .042). Although no significant links were shown with duration of stay (P = .232) and 30-day reoperation (P = .447), the multidisciplinary team participation was linked to a substantial decrease in perioperative mortality (P = .036) and postoperative complications (P = .002). Additionally, the multidisciplinary team group indicated stronger illness awareness and postoperative adherence among individuals with retroperitoneal liposarcoma. CONCLUSION: The study's findings indicate that multidisciplinary team management could result in improved clinical outcomes, higher diagnostic accuracy, and reduced duration of postoperative stays, complications, and perioperative mortality. The intervention may also enhance disease awareness and postoperative compliance in retroperitoneal liposarcoma patients who undergo surgery. However, evidence quality was deemed low, and prospective studies with robust designs are required. Nonetheless, these results are worth considering.
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Liposarcoma , Neoplasias Retroperitoneales , Humanos , Estudios Retrospectivos , Estudios Prospectivos , Liposarcoma/diagnóstico , Liposarcoma/cirugía , Neoplasias Retroperitoneales/cirugíaRESUMEN
Background: Surgery is the best way to cure the retroperitoneal leiomyosarcoma (RLMS), and there is currently no prediction model on RLMS after surgical resection. The objective of this study was to develop a nomogram to predict the overall survival (OS) of patients with RLMS after surgical resection. Methods: Patients who underwent surgical resection from September 2010 to December 2020 were included. The nomogram was constructed based on the COX regression model, and the discrimination was assessed using the concordance index. The predicted OS and actual OS were evaluated with the assistance of calibration plots. Results: 118 patients were included. The median OS for all patients was 47.8 (95% confidence interval (CI), 35.9-59.7) months. Most tumor were completely resected (n=106, 89.8%). The proportions of French National Federation of Comprehensive Cancer Centres (FNCLCC) classification were equal as grade 1, grade 2, and grade 3 (31.4%, 30.5%, and 38.1%, respectively). The tumor diameter of 73.7% (n=85) patients was greater than 5 cm, the lesions of 23.7% (n=28) were multifocal, and 55.1% (n=65) patients had more than one organ resected. The OS nomogram was constructed based on the number of resected organs, tumor diameter, FNCLCC grade, and multifocal lesions. The concordance index of the nomogram was 0.779 (95% CI, 0.659-0.898), the predicted OS and actual OS were in good fitness in calibration curves. Conclusion: The nomogram prediction model established in this study is helpful for postoperative consultation and the selection of patients for clinical trial enrollment.
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Leiomiosarcoma , Nomogramas , Humanos , Leiomiosarcoma/cirugía , Pronóstico , Estadificación de Neoplasias , Estimación de Kaplan-MeierRESUMEN
Introduction: The exploration of lipid metabolism dysregulation may provide novel perspectives for retroperitoneal liposarcoma (RPLS). In our study, we aimed to investigate potential targets and facilitate further understanding of immune landscape in RPLS, through lipid metabolism-associated genes (LMAGs) based prognostic model. Methods: Gene expression profiles and corresponding clinical information of 234 cases were enrolled from two public databases and the largest retroperitoneal tumor research center of East China, including cohort-TCGA (n=58), cohort-GSE30929 (n=92), cohort-FD (n=50), cohort-scRNA-seq (n=4) and cohort-validation (n=30). Consensus clustering analysis was performed to identify lipid metabolism-associated molecular subtypes (LMSs). A prognostic risk model containing 13 LMAGs was established using LASSO algorithm and multivariate Cox analysis in cohort-TCGA. ESTIMATE, CIBERSORT, XCELL and MCP analyses were performed to visualize the immune landscape. WGCNA was used to identify three hub genes among the 13 model LMAGs, and preliminarily validated in both cohort-GSE30929 and cohort-FD. Moreover, TIMER was used to visualize the correlation between antigen-presenting cells and potential targets. Finally, single-cell RNA-sequencing (scRNA-seq) analysis of four RPLS and multiplexed immunohistochemistry (mIHC) were performed in cohort-validation to validate the discoveries of bioinformatics analysis. Results: LMS1 and LMS2 were characterized as immune-infiltrated and -excluded tumors, with significant differences in molecular features and clinical prognosis, respectively. Elongation of very long chain fatty acids protein 2 (ELOVL2), the enzyme that catalyzed the elongation of long chain fatty acids, involved in the maintenance of lipid metabolism and cellular homeostasis in normal cells, was identified and negatively correlated with antigen-presenting cells and identified as a potential target in RPLS. Furthermore, ELOVL2 was enriched in LMS2 with significantly lower immunoscore and unfavorable prognosis. Finally, a high-resolution dissection through scRNA-seq was performed in four RPLS, revealing the entire tumor ecosystem and validated previous findings. Discussion: The LMS subgroups and risk model based on LMAGs proposed in our study were both promising prognostic classifications for RPLS. ELOVL2 is a potential target linking lipid metabolism to immune regulations against RPLS, specifically for patients with LMS2 tumors.
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Neoplasias Retroperitoneales , Humanos , Neoplasias Retroperitoneales/genética , Ecosistema , Metabolismo de los Lípidos , Pronóstico , Ácidos GrasosRESUMEN
Background: Although surgery plays a key role in the treatment of the primary retroperitoneal sarcoma (RPS), there remain few reports on the primary multifocal RPS. Aims: This study aimed to identify the prognostic factors for the primary multifocal RPS in an effort to optimize the clinical management of this malignancy. Methods: A retrospective analysis was conducted on a cohort of 319 primary RPS patients who underwent radical resection from 2009 to 2021, with post-operative recurrence as the primary endpoint of this study. COX regression was performed to identify the risk factors for post-operative recurrence, and a comparison was made to baseline and prognostic differences between multivisceral resection (MVR) and non-MVR groups with multifocal disease. Results: There were 31 (9.7%) patients with multifocal disease, the mean tumor burden placed on them was 24.1 ± 11.9 cm, and nearly half of the patients (48.4%) had MVR. Dedifferentiated liposarcoma, well-differentiated liposarcoma, and leiomyosarcoma accounted for 38.7%, 32.3%, and 16.1%, respectively. The 5-year recurrence-free survival rate reached 31.2% (95% CI, 11.2-51.2%) in the multifocal group and 51.8% (95% CI, 44.2-59.4%) in the unifocal group (P = 0.010). Age (heart rate [HR] = 0.916; P = 0.039) and complete resection (HR = 1.861; P = 0.043) were identified as the independent risk factors for the post-operative recurrence of multifocal primary RPS. Conclusions: Regarding primary multifocal RPS, the overall treatment strategy can be adopted for the treatment of the primary RPS, and MVR remains effective in boosting the chance of disease control for a selected group of patients. Relevance for Patients: This study is relevant to patients as it highlights the importance of receiving appropriate treatment for the primary RPS, especially for those with multifocal disease. The treatment options should be evaluated carefully to ensure that the patients receive the most effective treatment for their specific type and stage of RPS. The potential risk factors for post-operative recurrence should be well understood to minimize those risks. Ultimately, this study underscores the importance of ongoing research to optimize the clinical management of RPS and improve outcomes for patients.
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BACKGROUND: Surgery is the cornerstone of the treatment for primary retroperitoneal sarcoma (RPS). The purpose of this study was to establish a nomogram predictive model for predicting postoperative morbidity in primary RPS. METHODS: Clinicopathological data of patients who underwent radical resection from 2009 to 2021 were retrospectively analyzed. Risk factor analysis was performed using a logistic regression model, and modeling variables were selected based on Akaike Information Criterion. The nomogram prediction model was built on the basis of a binary logistic regression model and internally validated by calibration curves and concordance index. RESULTS: A total of 319 patients were enrolled, including 162 males (50.8%). 22.9% (n = 73) were over 65 years of age, and 70.2% (n = 224) had tumors larger than 10 cm. The most common histologic subtypes were well-differentiated liposarcoma (38.2%), dedifferentiated liposarcoma (25.1%) and leiomyosarcoma (7.8%). According to the Clavien-Dindo Classification, 96 (31.1%) and 31 (11.6%) patients had grade I-II complications and grade III-V complications, respectively. Age, tumor burden, location, operative time, number of combined organ resections, weighted resected organ score, estimated blood loss and packed RBC transfusion was used to construct the nomogram, and the concordance index of which was 0.795 (95% CI 0.746-0.844). and the calibration curve indicated a high agreement between predicted and actual rates. CONCLUSIONS: Nomogram, a visual predictive tool that integrates multiple clinicopathological factors, can help physicians screen RPS patients at high risk for postoperative complications and provide a basis for early intervention.
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Neoplasias Retroperitoneales , Sarcoma , Masculino , Humanos , Anciano , Nomogramas , Estudios Retrospectivos , Sarcoma/cirugía , Neoplasias Retroperitoneales/cirugía , MorbilidadRESUMEN
Background: Liposarcomas (LPS) are mesenchymal malignancies with four principal subtypes presenting distinct molecular and clinical features. Pleomorphic liposarcoma (PLPS) is one of the rarest and most aggressive subtypes of LPS. Surgical resection is currently a preferred curative approach for localized PLPS. However, the prognosis of unresectable PLPS is extremely poor, and there is no standard treatment. Case presentation: A 59-year-old Chinese woman was diagnosed with unresectable PLPS. The case was discussed and managed by specialists from a multidisciplinary team at Fudan Zhongshan Hospital. Preoperative radiotherapy (RT) of intensity-modulated radiation therapy (IMRT) at 50 Gy/25 Fx concurrently with the angiogenesis inhibitor anlotinib (8 mg, days 1-14, every 3 weeks) was prescribed to the patient. The dosage of anlotinib was increased to 10 mg after RT. After 6 months of treatment, the tumor had significantly shrunk and was successfully resected. Examination of the surgical specimens showed a pathological complete response (pCR). Until the latest follow-up (April 2022), no recurrence was observed, and disease-free survival has exceeded 14 months. Conclusion: This case sheds light on the probability that perioperative RT combined with an angiogenesis inhibitor can be effectively used in PLPS, which is resistant to chemotherapy and usually considered to have a poor prognosis. Further studies with randomized controlled clinical trials will improve our knowledge of this preoperative treatment strategy.
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Liposarcoma (LPS) is a rare and heterogeneous malignancy of adipocytic origin. Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are two of the most common subtypes, showing similar genetic characterizations but distinct biological behaviors and clinical prognosis. Compared to WDLPS, DDLPS is more aggressive and has the potential of metastasis, as the malignant adipocytic tumor's metabolic changes may have taken place during the tumorigenesis of LPSs. Therefore, to investigate the lipid alterations between the two subtypes, high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS) based untargeted lipidomic analysis was performed onto LPS tissues from 6 WDLPS and 7 DDLPS patients. The lipidomic analysis showed the upregulated phosphatidylcholines and phosphoethanolamines in DDLPS, and the upregulated triglycerides and diglycerides in WDLPS, which might be due to the uncompleted adipocytic dedifferentiation leading to such tumorigenesis. Such a finding was also confirmed by the similarity comparison of two LPS subtypes to the transcriptome of stromal vascular fraction at different differentiation stages. Transcriptomic analysis also demonstrated that metabolic pathways including the pentose phosphate pathway (PPP) were upregulated in WDLPS compared to DDLPS. Therefore, the cell line LPS853 was treated with the PPP inhibitor 6-aminonicotinamide ex vivo and the proliferation and invasion of LPS853 was significantly promoted by PPP inhibition, suggesting the potential role of PPP in the development and differentiation of LPS. In conclusion, this study described the altered lipid profiles of WDLPS and DDLPS for the first time, revealing the different differentiation stages of the two subtypes and providing a potential metabolic target for LPS treatment.
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OBJECTIVE: This investigation aimed to explore the relationship between sarcopenia and severe postoperative complications, relapse-free survival (RFS), and overall survival (OS) in patients with retroperitoneal liposarcoma (RLPS). MATERIAL AND METHODS: This retrospective study included 72 RLPS patients (47 men, 25 women; mean age, 57.49 years, SD 10.92) who had abdominal CT exams. Clinical information was recorded, including RLPS characteristics (histologic subtypes, grade, size), laboratory assessment (ALB, PALB, A/G, Hb, SCr), relapse-free survival, overall survival, and postoperative complications. The relationships between those variables and RFS and OS were analyzed using Cox proportional hazard models. RESULTS: There were 8 severe postoperative complications (Clavien-Dindo grade > 2). The chi-square test showed sarcopenia was associated with severe postoperative complications (P = 0.011). In multivariate analysis, sarcopenia was not associated with relapse-free survival (P = 0.574) and overall survival (P = 0.578). CONCLUSIONS: Sarcopenia predicts worse surgical complications but does not affect relapse-free survival and overall survival.
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Liposarcoma , Neoplasias Retroperitoneales , Sarcopenia , Masculino , Humanos , Femenino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Neoplasias Retroperitoneales/complicaciones , Neoplasias Retroperitoneales/cirugía , Liposarcoma/complicaciones , Liposarcoma/cirugía , Sarcopenia/complicaciones , Enfermedad Crónica , Complicaciones PosoperatoriasRESUMEN
BACKGROUND: Distal duodenal resections are sometimes necessary for radical surgery, but how to restore duodenal continuity is still unclear. This study aimed at determining which style of anastomosis was more suitable for the duodenojejunostomy after resection of distal duodenum. PATIENTS AND METHODS: We retrospectively identified 34 patients who underwent distal duodenum resection at our center between January 2014 and December 2021. According to whether the end or the side of the proximal duodenum was involved in reconstruction, duodenojejunostomy were classified as End style (E-style) and Side style (S-style). Demographic data, clinicopathological details, and postoperative complications were analyzed between two groups. RESULTS: Thirteen patients (38.2%) received E-style duodenojejunostomy, and 21 patients (62.8%) received S-style duodenojejunostomy. Comparative analysis showed that in group of E-style, patients had a lower rate of multivisceral resection(5/13 vs 18/21; P = 0.008), delayed gastric emptying (DGE) (1/13 vs 11/21; P = 0.011) and intraperitoneal infection (2/13 vs 12/21; P = 0.03). In this study, the incidence of major complications was up to 35.3% (12/34) and no patient died of complication in perioperative period. In two group, there was no difference in the incidence of major complications (E-style vs S-style: 3/13 vs 9/21; P = 0.292). CONCLUSIONS: The E-style duodenojejunostomy for the reconstruction of distal duodenum resection is safe and feasible. The E-style anastomosis may have potential value in decreasing the occurrence of complications such as DGE and intraperitoneal infection, and the definitive advantages still need to be verified.
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Duodeno , Pancreaticoduodenectomía , Humanos , Estudios Retrospectivos , Duodeno/cirugía , Anastomosis Quirúrgica , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugíaRESUMEN
The mainstay of treatment for primary retroperitoneal sarcoma (RPS) is surgery. However, whether multiple visceral resection (MVR) affects patients' quality of life compared with simple tumor resection has not been reported. Patients with primary RPS who underwent radical resection between 2009 and 2021 were included. Patients who were alive at the last follow-up were asked to complete the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). The primary endpoint of the study was the global health (GH) score. A total of 161 patients were included, including 77 in the MVR group and 84 in the non-MVR group. When comparing EORTC scores on functional domains and symptom scales between MVR and non-MVR groups, only constipation scores differed (p = 0.011). Comparing GH scores within 6 months after surgery between the two groups, GH was better in non-MVR patients (58.3 vs. 76.4, p = 0.082). However, patients with longer postoperative intervals in the MVR group had higher scores (p < 0.001), and patients with postoperative intervals of more than one year scored similar to those in the non-MVR group (64.7 vs. 59.2, p = 0.522). As the postoperative interval increased, there was an improvement in all indicators in MVR patients, while there was no significant improvement in non-MVR patients. Aggressive surgical approaches impair quality of life within 6 months postoperatively, but the long-term quality of life is similar to that of patients undergoing simple tumor resection. This should be factored into RPS treatment decisions.
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Background: There are lacking standard treatment guidelines for aggressive fibromatosis (AF) because of its rarity. Aim: This study aimed to investigate the risk factors for recurrence and survival of abdominal AF after radical surgical resection. Methods: From August 2012 to December 2020, a retrospective analysis was conducted on the clinical data of 69 AF in Shanghai Public Health Clinical Center Affiliated to Fudan University, with the tumor locating either in the abdominal wall or in the abdominal cavity. The main observation end point was progression-free survival time (PFS) and overall survival time (OS). Results: All 69 patients achieved microscopic R0 resection, 10 (14.5%) had local recurrence, and 3 (4.3%) died. The PFS rate after 1, 3, 5, and 10 years was 96.8%, 87.7%, 78.8%, and 78.8%, respectively. The OS rate after 1, 3, 5, and 10 years was 100%, 100%, 92.9%, and 81.3%, respectively. In 10 patients with recurrence, the median recurrence time was 17.6 months. Concomitant familial adenomatous polyposis (FAP) and history of previous recurrence were independent risk factors of post-operative recurrence. Conclusion: After radical surgery of abdominal AF, the local recurrence rate was 15%. Concomitant FAP and a previous history of recurrence were independent risk factors of post-operative recurrence. R0 and a combined organ resection should be performed especially in FAP patients to minimize the recurrence and improve the prognosis. Relevance for Patients: The present study identifies the risk factors of recurrence in AF and suggests R0 resection especially in concomitant FAP patients. A wait-and-see strategy should not be generally implemented and radical surgery will bring clinical benefits to patients with such kind of rare disease.
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Introduction: Cowden syndrome is a rare autosomal dominant genetic disease associated with PTEN mutation and is mainly shown as systemic multisystem lesions. The incidence of adenocarcinoma of the duodenum with Cowden syndrome in Asian males is rare. We hereby describe the diagnosis, treatment, and prognosis of a patient with duodenal carcinoma and Cowden syndrome. Case Description: A 40-year-old Chinese man was hospitalized because of gastrointestinal hemorrhage and anemia due to infiltrating adenocarcinoma of the descending part of the duodenum. He also had typical signs of Cowden syndrome, such as multiple polyps of the gastrointestinal tract, macrocephaly, papilloma of the tongue, soles hyperkeratosis, and melanosis spots. After the pancreaticoduodenectomy (classic Whipple), the lesions revealed the presence of hamartomatoid polyps, and some of them mutated into non-mucinous adenocarcinoma (80%) and mucinous adenocarcinoma (20%). Further investigation showed a lack of PTEN protein expression in the duodenal neoplasm, and genetic analysis showed the mutation of p.E242fs in PTEN. The patient was followed up for 1 year. There was no appearance of recurrence or distant metastasis. Conclusion: It is suggested that we should pay more attention to the differential diagnosis of duodenal carcinoma combined with gastrointestinal polyps. If multiple gastrointestinal polyps with gastrointestinal bleeding are encountered, Cowden syndrome should be considered, and timely diagnosis and treatment should be implemented.
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Liver metastasis is a leading indicator of poor prognosis in patients with colorectal cancer (CRC). Exosomal intercellular communication has been reported to play an important role in cancer invasion and metastasis. Here, we characterized exosomal miRNAs underlying liver metastasis in CRC patients (Cohort 1, n = 30) using miRNA arrays. Exosomal miR-150 was found to be downregulated in CRC patients with liver metastases compared to those without (P = 0.025, fold change [FC] = 2.01). These results were then validated using another independent cohort of CRC patients (Cohort 2, n = 64). Patients with low expression of exosomal miR-150 had significantly shorter overall survival (OS) time (33.3 months versus 43.3 months, P = 0.002). In addition, the low expression of exosomal miR-150 was significantly correlated with advanced tumor node metastasis staging (P = 0.013), higher CA199 level (P = 0.018), and the presence of liver metastasis (P = 0.048). Multivariate analysis showed that low expression of exosomal miR-150 (P = 0.035) and liver metastasis (P < 0.001) were independent prognostic factors for overall survival. In vivo and in vitro studies showed that the viability and invasion of CRC cells were both significantly suppressed by ExomiR-150. Target-prediction assessment and dual-luciferase reporter assay indicated that FTO (the fat mass and obesity-associated gene) was a direct target for miR-150. This study first demonstrated that exosomal miR-150 may be a potential prognostic factor and treatment target for CRC.
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Neoplasias Colorrectales , Exosomas , Neoplasias Hepáticas , MicroARNs , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/metabolismo , Pronóstico , Exosomas/metabolismo , Regulación Neoplásica de la Expresión Génica , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genéticaRESUMEN
BACKGROUND: Most retroperitoneal sarcoma (RPS) operations require combined multi-organ resection, and the proportion of unplanned reoperation is high. However, there are no relevant studies on reoperation for RPS. METHODS: Patients who underwent at least once unplanned reoperation at Shanghai Public Health Clinical Center, Fudan University, China, from August 2009 to December 2021 were retrospectively analyzed. The baseline characteristics, primary surgery, and reoperation information, postoperative complications, and survival were analyzed. RESULTS: A total of 51 patients were included. Among them, 21 (41.2%) were male and 30 (58.8%) were female. The median age was 51 (interquartile range [IQR], 49-63) years. Most (88.3%) had a history of abdominal surgery. Dedifferentiated liposarcoma, well-differentiated liposarcoma, leiomyosarcoma, and others accounted for 50.9%, 21.6%, 15.7%, and 11.8%, respectively. The conditions of the primary operation were as follows: 35 (68.6%) patients achieved complete surgical resection, 48 patients had combined organ resection, and a median of 3 (IQR, 2-4) organs was removed, of which 5 (9.9%) were combined with pancreaticoduodenectomy. The median operative time was 330 (IQR, 245-440) min, and the median estimated blood loss was 1500 (IQR, 500-2600) ml. The median postoperative hospital stay was 42 (IQR, 23-82) days. For reoperation, the most common reasons were bleeding (31.3%), complications related to intestinal anastomosis (27.4%), and intestinal perforation (19.9%). The mortality rate after reoperation was 39.2% (20/51). Twelve (23.5%) patients underwent reoperation at least twice. CONCLUSIONS: Unplanned reoperation among retroperitoneal sarcoma correlates with established measures of surgical quality.
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Neoplasias Retroperitoneales , Sarcoma , Neoplasias de los Tejidos Blandos , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Reoperación , Neoplasias Retroperitoneales/cirugía , Estudios Retrospectivos , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/cirugía , Tasa de SupervivenciaRESUMEN
Objective: This study aimed to explore the prognostic factors for first local recurrent retroperitoneal soft tissue sarcoma (FLR-RPS) and construct predictive nomograms in the Asian population. Methods: In a single Asian sarcoma center, data of patients with FLR-RPS were retrospectively analyzed from January 2011 to September 2020. We developed and internally validated prognostic factors determined by the Cox regression model, as well as nomograms for predicting recurrence-free survival (RFS) and overall survival (OS). The concordance index and calibration curve were used to determine the nomogram's discriminative and predictive ability. Results: With 169 patients, the median follow-up duration was 48 months and the 5-year OS rate was 60.9% (95% confidence interval (CI), 51.9%-69.9%). OS was correlated with chemotherapy at the time of initial surgery and tumor grading. The 5-year cumulative local recurrence rate and distant metastasis rate were 75.9% (95% CI, 67.5%-84.3%) and 10.1% (95% CI, 4.2%-16.0%), respectively, and the length of the disease-free interval following the primary operation was associated with disease recurrence. The 6-year OS and cumulative recurrence rate after surgery in our cohort were comparable with those in the TARPSWG cohort, but the proportion of local recurrence was higher (80.4% vs. 59.0%), and distant metastasis was less common (10.1% vs. 14.6%). In this study, two nomogram prediction models were established, which could predict the 1-, 2-, and 5-year OS and RFS, and the concordance indices were 0.74 and 0.70, respectively. The calibration plots were excellent. Conclusions: For the FLR-RPS patients, some can still achieve an ideal prognosis. The treatment of FLR-RPS in Asian populations can be aided by the predictive model established in this study.
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Background: This study aimed to investigate the clinicopathological characteristics of retroperitoneal solitary fibrous tumor (RSFT) and the safety of radical resection. Methods: A retrospective analysis was conducted on the data of 32 RSFT patients who received surgery with curative intent from February 2011 and June 2021. Results: This cohort included 16 (50%) male and 16 (50%) female patients, with the median age of 52 (29 to 72) years. Tumor burden ranged from 3 to 25 (median, 10) cm. Seven patients received arterial embolization before surgery. 15 (47%) patients received radiotherapy, nine (28%) of which received preoperative radiotherapy. Most of the patients (91%) achieved complete resection with median bleeding of 400 (20 to 5,000) ml. Nine (28%) patients received packed red blood cell (RBC) transfusion, with a median of 5 (2 to 10) U. All patients had the five-year progression-free survival rate and the overall survival rate of 75.8% and 80.0%, respectively. 11 (34%) patients were found with adverse events, and four (12%) patients were found with serious postoperative complications (Clavien-Dindo ≥3), of which one (3.1%) patient died after surgery. The univariate analysis found that tumor burden (p = 0.022), packed RBC transfusion (p = 0.001) and postoperative hospital stays (0.027) were correlated with overall morbidity. The multivariate analysis found packed RBC transfusion as an independent risk factor for postoperative morbidity (HR 381.652, 95% CI, 1.597-91213.029, p = 0.033). Conclusion: RSFT was confirmed as an uncommon, slow-growing and recurring tumor, with acceptable postoperative morbidity and mortality after surgical resection.
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BACKGROUND: Leiomyosarcoma (LMS) is a malignant smooth muscle neoplasm, in which the efficacy of immune checkpoint blockade (ICB) is very limited. What is worse, loss of PTEN, known as a negative factor for ICB, frequently occurred in LMS. Seeking new strategies for LMS patients harboring loss of PTEN is important and challenging. CASE PRESENTATION: A 42-year-old Chinese male was diagnosed as having unresectable LMS of the iliopsoas. After the failure of two prior chemotherapy regimens, whole-exome sequencing revealed that tumor tissue had high tumor mutation burden (689 Muts), high microsatellite instability, and some somatic mutations, including PTEN (copy number loss and p.N323fs), MSH6 (p.F1088fs), TP53 p.R273C, ASXL1 p.G645fs, ATR p.S1843P, and CDKN2A p.A118P. Then, antiangiogenic agent (pazopanib or anlotinib) plus pembrolizumab was administered from January 2 to August 6, 2018. However, pazopanib was stopped on June 18 due to the grade 2/3 adverse effect of hand-foot skin reaction, and anlotinib was administered. Considering that the tumor shrunk after immunotherapy, he underwent radical resection on September 6, 2018. The final pathological diagnosis confirmed pathologic complete response (CR). Until the latest follow-up (September 15, 2021), no progressive disease was observed and total disease-free survival has exceeded 36 months. CONCLUSION: We presented a patient with an unresectable mismatch repair (MMR)-deficient LMS harboring biallelic loss of PTEN who achieved CR from a combination strategy of antiangiogenesis plus pembrolizumab. Such a strategy might be a promising strategy to overcome the ICB resistance caused by the loss of PTEN. Such conclusions need to be further confirmed in further investigations.
RESUMEN
BACKGROUND: Management of retroperitoneal sarcoma (RPS) involving the iliac artery is challenging and requires the concerted efforts of multidisciplinary team (MDT) members during surgical treatment. AIM: To summarize the clinicopathologic features of RPS involving the iliac artery and our retroperitoneal soft tissue tumor MDT surgical experience. METHODS: In this retrospective study, 15 patients with RPS involving the iliac artery who underwent surgery at our retroperitoneal soft tissue tumor center from July 2004 to June 2020 were analyzed. Statistical analyses were performed by Student's t-test with SPSS 16.0. RESULTS: Complete tumor resection (R0/R1) and iliac artery reconstruction were achieved in all 15 patients. All the operations were successful, with no serious complications or perioperative death. Resection with bilateral iliac artery reconstruction required a higher intraoperative blood transfusion volume than resection with unilateral iliac artery reconstruction. Recurrent cases were more likely to bleed and required a higher blood transfusion volume than primary cases. As of January 2021, 11 patients were alive, and 4 had died. Local recurrence occurred in two patients, one of whom developed liver metastasis. CONCLUSION: Resection of RPS involving iliac vessels is feasible and effective when performed by MDT members. Iliac artery oncovascular resection and reconstruction are key to a successful operation. Adequate blood preparation is important for successful completion of surgery.