Development and validation of a nomogram for predicting morbidity in surgically resected primary retroperitoneal sarcoma.

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.

Association of RAS/BRAF Status and Prognosis of Metastatic Colorectal Cancer: Analysis of 1002 Consecutive Cases.

BACKGROUND: This study aimed to analyze the association of RAS/BRAF status and the prognosis of patients with metastatic colorectal cancer (mCRC) based on multi-disciplinary team (MDT) treatment mode. METHODS: The study retrospectively analyzed 1002 consecutive mCRC patients with different tumor RAS/BRAF status at Zhongshan Hospital Fudan University from April 2012 to December 2018. The association of RAS/BRAF status with clinicopathologic features and prognosis was analyzed. RESULTS: The mutation rate was 42.3% (424/1002) for RAS and 5.0% (50/1002) for BRAF. The RAS and BRAF mutations were mutually exclusive of each other. An association of RAS/BRAF status with sex (P < 0.001), age (P = 0.021), primary tumor location (P < 0.001), pathologic type (P < 0.001), differentiation (P < 0.001), metastatic organ (P < 0.001), carcinoembryonic antigen (CEA) (P < 0.001), and cancer antigen (CA)19-9 (P < 0.001) was observed. Overall survival (OS) was better for the RAS/BRAF wild-type patients than for the RAS-mutant patients, whereas the BRAF-mutant patients had the worst OS (51.0 vs 34.9 vs 18.9 months; P < 0.001). Regardless of RAS/BRAF status, metastases resection significantly improved OS (64.0 vs. 21.3 months; P < 0.001). Among the initially unresectable patients, the RAS/BRAF wild-type patients had a better conversional resection rate (32.9% vs 19.1% vs 0; P < 0.001) and a better OS (33.8 vs 23.3 vs 13.2 months; P = 0.005) than the RAS- and BRAF-mutant patients. Similarly, among the initially resectable patients, the RAS/BRAF wild-type patients had a better OS than the RAS- or BRAF- mutant patients (not assessable vs 51.7 vs 35.4 months; P = 0.005). CONCLUSIONS: This large-sample study showed that regardless of metastases resection or no resection, RAS and BRAF mutations were associated with a poor prognosis. Resection of metastases could bring survival benefits for patients regardless of RAS/BRAF status.

Unplanned reoperation after resection of retroperitoneal sarcoma: experience based on a high-volume sarcoma center.

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.

Sarcopenia is associated with worse surgical complications but not relapse-free survival and overall survival in patients with retroperitoneal liposarcoma.

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.

Which style of duodenojejunostomy is better after resection of distal duodenum.

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.

High patatin like phospholipase domain containing 8 expression as a biomarker for poor prognosis of colorectal cancer.

BACKGROUND: Patatin like phospholipase domain containing 8 (PNPLA8) has been shown to play a significant role in various cancer entities. Previous studies have focused on its roles as an antioxidant and in lipid peroxidation. However, the role of PNPLA8 in colorectal cancer (CRC) progression is unclear. AIM: To explore the prognostic effects of PNPLA8 expression in CRC. METHODS: A retrospective cohort containing 751 consecutive CRC patients was enrolled. PNPLA8 expression in tumor samples was evaluated by immunohistochemistry staining and semi-quantitated with immunoreactive scores. CRC patients were divided into high and low PNPLA8 expression groups based on the cut-off values, which were calculated by X-tile software. The prognostic value of PNPLA8 was identified using univariate and multivariate Cox regression analysis. The overall survival (OS) rates of CRC patients in the study cohort were compared with Kaplan-Meier analysis and Log-rank test. RESULTS: PNPLA8 expression was significantly associated with distant metastases in our cohort (P = 0.048). CRC patients with high PNPLA8 expression indicated poor OS (median OS = 35.3, P = 0.005). CRC patients with a higher PNPLA8 expression at either stage I and II or stage III and IV had statistically significant shorter OS. For patients with left-sided colon and rectal cancer, the survival curves of two PNPLA8-expression groups showed statistically significant differences. Multivariate analysis also confirmed that high PNPLA8 expression was an independent prognostic factor for overall survival (hazard ratio HR = 1.328, 95%CI: 1.016-1.734, P = 0.038). CONCLUSION: PNPLA8 is a novel independent prognostic factor for CRC. These findings suggest that PNPLA8 is a potential target in clinical CRC management.

Multi-omics joint analysis revealed the metabolic profile of retroperitoneal liposarcoma.

Retroperitoneal liposarcoma (RLPS) is the main subtype of retroperitoneal soft sarcoma (RSTS) and has a poor prognosis and few treatment options, except for surgery. The proteomic and metabolic profiles of RLPS have remained unclear. The aim of our study was to reveal the metabolic profile of RLPS. Here, we performed proteomic analysis (n = 10), metabolomic analysis (n = 51), and lipidomic analysis (n = 50) of retroperitoneal dedifferentiated liposarcoma (RDDLPS) and retroperitoneal well-differentiated liposarcoma (RWDLPS) tissue and paired adjacent adipose tissue obtained during surgery. Data analysis mainly revealed that glycolysis, purine metabolism, pyrimidine metabolism and phospholipid formation were upregulated in both RDDLPS and RWDLPS tissue compared with the adjacent adipose tissue, whereas the tricarboxylic acid (TCA) cycle, lipid absorption and synthesis, fatty acid degradation and biosynthesis, as well as glycine, serine, and threonine metabolism were downregulated. Of particular importance, the glycolytic inhibitor 2-deoxy-D-glucose and pentose phosphate pathway (PPP) inhibitor RRX-001 significantly promoted the antitumor effects of the MDM2 inhibitor RG7112 and CDK4 inhibitor abemaciclib. Our study not only describes the metabolic profiles of RDDLPS and RWDLPS, but also offers potential therapeutic targets and strategies for RLPS.

Multivisceral resection of primary multifocal retroperitoneal sarcomas: a retrospective study from a high-volume sarcoma center.

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.

Identification of MDM2 as a prognostic and immunotherapeutic biomarker in a comprehensive pan-cancer analysis: A promising target for breast cancer, bladder cancer and ovarian cancer immunotherapy.

BACKGROUND: The murine double minute 2 (MDM2) gene is a crucial factor in the development and progression of various cancer types. Multiple rigorous scientific studies have consistently shown its involvement in tumorigenesis and cancer progression in a wide range of cancer types. However, a comprehensive analysis of the role of MDM2 in human cancer has yet to be conducted. METHODS: We used various databases, including TIMER2.0, TCGA, GTEx and STRING, to analyze MDM2 expression and its correlation with clinical outcomes, interacting genes and immune cell infiltration. We also investigated the association of MDM2 with immune checkpoints and performed gene enrichment analysis using DAVID tools. RESULTS: The pan-cancer MDM2 analysis found that MDM2 expression and mutation status were observably different in 25 types of cancer tissue compared with healthy tissues, and prognosis analysis showed that there was a significant correlation between MDM2 expression and patient prognosis. Furthermore, correlation analysis showed that MDM2 expression was correlated with tumor mutational burden, microsatellite instability and drug sensitivity in certain cancer types. We found that there was an association between MDM2 expression and immune cell infiltration across cancer types, and MDM2 inhibitors might enhance the effect of immunotherapy on breast cancer, bladder cancer and ovarian cancer. CONCLUSIONS: The first systematic pan-cancer analysis of MDM2 was conducted, and it demonstrated that MDM2 was a reliable prognostic biomarker and was closely related to cancer immunity, providing a potential immunotherapeutic target for breast cancer, bladder cancer and ovarian cancer.

Proteomic characteristics reveal the signatures and the risks of T1 colorectal cancer metastasis to lymph nodes.

The presence of lymph node metastasis (LNM) affects treatment strategy decisions in T1NxM0 colorectal cancer (CRC), but the currently used clinicopathological-based risk stratification cannot predict LNM accurately. In this study, we detected proteins in formalin-fixed paraffin-embedded (FFPE) tumor samples from 143 LNM-negative and 78 LNM-positive patients with T1 CRC and revealed changes in molecular and biological pathways by label-free liquid chromatography tandem mass spectrometry (LC-MS/MS) and established classifiers for predicting LNM in T1 CRC. An effective 55-proteins prediction model was built by machine learning and validated in a training cohort (N=132) and two validation cohorts (VC1, N=42; VC2, N=47), achieved an impressive AUC of 1.00 in the training cohort, 0.96 in VC1 and 0.93 in VC2, respectively. We further built a simplified classifier with nine proteins, and achieved an AUC of 0.824. The simplified classifier was performed excellently in two external validation cohorts. The expression patterns of 13 proteins were confirmed by immunohistochemistry, and the IHC score of five proteins was used to build an IHC predict model with an AUC of 0.825. RHOT2 silence significantly enhanced migration and invasion of colon cancer cells. Our study explored the mechanism of metastasis in T1 CRC and can be used to facilitate the individualized prediction of LNM in patients with T1 CRC, which may provide a guidance for clinical practice in T1 CRC.

Most patients with early-stage colorectal cancer can be treated with a minimally invasive procedure. Surgeons use a flexible tool to remove precancerous or cancerous cells, cutting the risk of death from colorectal cancer in half. But a small number of early-stage colorectal cancer patients are at risk of their cancer spreading to the lymph nodes. These patients need more extensive surgery. Clinicians use risk stratification tools to decide which patients need more extensive surgery. Unfortunately, the existing risk stratification tools are not very accurate. The current approach, which analyzes colon tissue for cancerous changes, classifies 70% to 80% of early-stage colorectal cancer patients as high risk for cancer spread. But only about 8% to 16% of patients in the high risk group have lymph node metastasis. As a result, many patients undergo unnecessary, invasive surgery. Zhuang, Zhuang, Chen, Qin, et al. developed a more accurate way to predict which patients are at risk of lymph node metastasis using proteins. In the experiments, the team analyzed the proteins in tumor samples from 143 patients with early colorectal cancer who did not have lymph node metastases and 78 patients with metastases. Zhuang et al. then used machine learning to build a prediction tool that used 55 proteins to identify patients at risk of metastases. The new approach was more accurate than existing tools and simplified versions with only nine or five proteins also performed better than existing tools. This work provides preliminary evidence that protein-based models using as few as five proteins can more accurately identify which patients are at risk of metastasis. These models may reduce the number of patients who undergo unnecessary invasive surgery. The experiments also identified potential targets for therapies to prevent or treat lymph metastases. For example, they showed that low levels of the RHOT2 protein predict metastasis.

Nomogram development and external validation for predicting overall survival and cancer-specific survival in patients with primary retroperitoneal sarcoma: a retrospective cohort study.

BACKGROUND: Primary retroperitoneal sarcoma (RPS) comprises over 70 histologic subtypes, yet there are limited studies that have developed prognostic nomograms for RPS patients to predict overall survival (OS) and cancer-specific survival (CSS). The objective of this study was to construct prognostic nomograms for predicting OS and CSS in RPS patients. METHODS: We identified a total of 1166 RPS patients from the Surveillance, Epidemiology and End Results (SEER) database, and an additional 261 cases were collected from a tertiary cancer center. The study incorporated various clinicopathological and epidemiologic features as variables, and prediction windows for overall survival (OS) and cancer-specific survival (CSS) were set at 3, 5, and 7 years. Multivariable Cox models were utilized to develop the nomograms, and variable selection was performed using a backward procedure based on the Akaike Information Criterion. To evaluate the performance of the nomograms in terms of calibration and discrimination, we used calibration plots, coherence index, and area under the curve. FINDINGS: The study included 818 patients in the development cohort, 348 patients in the internal validation cohort, and 261 patients in the external validation cohort. The backward procedure selected the following variables: age, French Federation of Cancer Centers Sarcoma Group (FNCLCC) grade, pre-/postoperative chemotherapy, tumor size, primary site surgery, and tumor multifocality. The validation results demonstrated that the nomograms had good calibration and discrimination, with C-indices of 0.76 for OS and 0.81 for CSS. Calibration plots also showed good consistency between the predicted and actual survival rates. Furthermore, the areas under the time-dependent receiver operating characteristic curves for the 3-, 5-, and 7-year OS (0.84, 0.82, and 0.78, respectively) and CSS (0.88, 0.88, and 0.85, respectively) confirmed the accuracy of the nomograms. INTERPRETATION: Our study developed accurate nomograms to predict OS and CSS in patients with RPS. These nomograms have important clinical implications and can assist healthcare providers in making informed decisions regarding patient care and treatment options. They may also aid in patient counseling and stratification in clinical trials.

Cancer-Associated Fibroblast-Derived Exosomal miRNA-320a Promotes Macrophage M2 Polarization In Vitro by Regulating PTEN/PI3Kγ Signaling in Pancreatic Cancer.

Our previous study has indicated that cancer-associated fibroblasts (CAFs) play a crucial role in regulating gemcitabine resistance through transferring exosomal miRNA-106b to cancer cells. Tumor-associated macrophages (TAMs) are recently verified to facilitate gemcitabine resistance. However, the effect of CAFs in regulating TAMs function in pancreatic cancer (PCa) remains unclear. Here, primary CAFs were extracted from tumor tissues of PCa patients, and CAFs-derived exosomes (CAFs-Exo) were acquired and authenticated by transmission electron microscopy, qNano, and western blot analysis. The role of exosomal miRNA-320a in facilitating macrophage M2 polarization was investigated in vitro. We found that CAFs-derived conditioned medium (CM) possessed a higher potential to promote macrophage M2 polarization compared with normal fibroblasts (NFs) or PCa cell-derived CM. Furthermore, CAFs-Exo treatment polarized macrophage to M2 phenotype. miRNA-320a levels were remarkably increased in CAFs-Exo versus NFs-Exo. More important, miRNA-320a could be transferred from CAFs to macrophages through exosomes, and miRNA-320a overexpression in macrophages facilitated its M2 polarization. Functionally, miRNA-320a-overexpressed macrophages facilitated PCa cell proliferation and invasion. CAFs pretreated with miRNA-320a inhibitor reduced miRNA-320a expression in CAFs-Exo and led to decreased M2 macrophage polarization. Finally, we verified that miRNA-320a polarized macrophage to M2 phenotype by regulating PTEN/PI3Kγ signaling. Taken together, the current data demonstrated that CAFs-derived exosomal miRNA-320a facilitated macrophage M2 polarization to accelerate malignant behavior of PCa cells.

Prognostic Factors and Nomogram Construction for First Local Recurrent Retroperitoneal Sarcoma Following Surgical Resection: A Single Asian Cohort of 169 Cases.

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.

Postoperative Morbidity After Radical Resection of Retroperitoneal Solitary Fibrous Tumor.

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.

Case Report: Duodenal Carcinoma in a 40-Year-Old Asian Man With Cowden Syndrome.

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.

Does Aggressive Surgery Mean Worse Quality of Life and Functional Capacity in Retroperitoneal Sarcoma Patients?-A Retrospective Study of 161 Patients from China.

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.

Risk factors for recurrence of abdominal aggressive fibromatosis after radical surgery: An 8-year observational study from a chinese high-volume sarcoma center.

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.

Tumor grade and symptoms at presentation are survival risk factors in Chinese patients with primary retroperitoneal sarcoma.

Background and Aim: No cohort studies have been performed on Chinese primary retroperitoneal sarcoma (RPS) patients. Data derived from western cohort studies may not be directly superimposable on Asian counterparts. Furthermore, the risk factors for survival of RPS are currently unknown for Chinese patients. The objectives were therefore to (1) gain insight into RPS incidence and patient demographics and clinical details; (2) determine the risk factors for overall survival (OS) and disease-free survival (DFS); and (3) critically appraise the Asian cohort data in relation to information obtained in western cohort studies. Methods: In this retrospective cohort study, the health records of patients that had been diagnosed with primary localized RPS with curative intent between 2009 and 2020 were analyzed. Cox proportional hazards analysis was conducted to evaluate the risk factors for OS and DFS. Results: A total of 261 patients met the inclusion criteria. Ninety-six (36.8%) patients had been diagnosed with well-differentiated liposarcoma, 63 patients (24.1%) with dedifferentiated liposarcoma, 41 patients (15.7%) with leiomyosarcoma (LMS), 22 patients (8.4%) with solitary fibroma, 7 patients (2.7%) with malignant peripheral nerve sheath tumor (MPNST), and 32 patients (12.3%) with another type of RPS. The study further revealed that (1) the 5-y OS and DFS in RPS patients was 67.8% and 51.3%, respectively, with the highest OS and DFS observed in MPNST (100% and 100%, respectively) and the lowest 5-y OS and DFS attributed to LMS (42.6% and 28.9%, respectively); (2) symptoms at presentation, Federal National Cancer Center (FNCLCC) grade, and number of combined resections are independent risk factors in OS; (3) symptoms at presentation, FNCLCC grade, chemotherapy, and hospital length of stay are independent risk factors for DFS; and (4) patients at high risk (symptoms at presentation and high-grade tumors) have less than half the chance of survival at 5 y post-diagnosis than patients with a low-risk profile. Conclusions: Symptoms at presentation constitute a risk factor for OS and DFS. When combined with tumor grade - another risk factor for both OS and DFS - patients can be classified into a high-risk and low-risk category to gauge a patient's prognosis and, accordingly, frame an optimal clinical trajectory. Moreover, the clinicopathology and overall prognosis of RPS in Asian and Western populations are comparable and hence superimposable. Relevance for Patients: The present study identifies the risk factors of survival in RPS and suggests symptoms at presentation should be considered in the preoperative consultation and added in prognostic grouping.

Development and Validation of a Nomogram for Predicting Recurrence-Free Survival of Surgical Resected Retroperitoneal Liposarcoma.

BACKGROUND AND OBJECTIVES: Surgical treatment is still the mainstay of curative therapy for retroperitoneal liposarcoma (RLPS), but often recurs after surgical resection. We aimed to establish a nomogram for postoperative recurrence of RLPS based on the Asian population. METHODS: Patients after surgical resection at the South Hospital of Zhongshan Hospital/Shanghai Public Health Clinical Center between August 2011 and December 2020 were included. The enrolled patients are randomly divided into training set and test set according to the ratio of 7:3. Prognostic factors were chosen based on Akaike Information Criterion, and the nomogram was built based on Cox regression and then internally validated through calibration plots and concordance index (C-index). RESULTS: A total of 447 patients were included. Gender, age, presentation status, organ invasion and FNCLCC grade were used to build nomogram. The calibration plots showed that RFS predicted probabilities are identical to the actual RFS rates. The C-index of the nomogram was 0.703 (95% CI 0.623-0.783) in the training set and 0.695 (95% CI 0.565-0.825) in test set. CONCLUSION: The nomogram we established can accurately predict postoperative recurrence of RLPS patients for Asian population.