circNEIL3 inhibits tumor metastasis through recruiting the E3 ubiquitin ligase Nedd4L to degrade YBX1.

Distant metastasis is a major contributor to cancer-related mortality. However, the role of circRNAs in this process remains unclear. Herein, we profiled the circRNA expression in a cohort of 68 colorectal carcinoma (CRC) primary tumors and their paired liver metastatic lesions. By overlapping with the TGFß-responsive circRNAs, circNEIL3 (hsa_circ_0001460) was identified as a TGFß-repressive and metastasis-related circRNA. Functionally, circNEIL3 effectively inhibited tumor metastasis in both and in vivo and in vivo models of various cancer types. Mechanistically, circNEIL3 exerts its metastasis-repressive function through its direct interaction with oncogenic protein, Y-box-binding protein 1 (YBX1), which consequently promotes the Nedd4L-mediated proteasomal degradation of YBX1. Importantly, circNEIL3 expression was negatively correlated to YBX1 protein level and metastatic tendency in CRC patient samples. Collectively, our findings indicate the YBX1-dependent antimetastatic function of circNEIL3 and highlight the potential of circNEIL3 as a biomarker and therapeutic option in cancer treatment.

JMJD3 Is Required for Acute Pancreatitis and Pancreatitis-Associated Lung Injury.

Acute pancreatitis (AP) can be complicated by inflammatory disorders of remote organs, such as lung injury, in which Jumonji domain-containing protein 3 (JMJD3) plays a vital role in proinflammatory responses. Currently, we found that JMJD3 expression was upregulated in the pancreas and lung in an AP male mouse model, which was also confirmed in AP patients. Further experiments revealed that the upregulation of JMJD3 and proinflammatory effects were possibly exerted by mitochondrial DNA (mtDNA) or oxidized-mtDNA from tissue injury caused by AP. The release of mtDNA and oxidized-mtDNA contributed to the infiltration of inflammatory monocytes in lung injury through the stimulator of IFN genes (STING)/TLR9-NF-κB-JMJD3-TNF-α pathway. The inhibition of JMJD3 or utilization of Jmjd3-cKO mice significantly alleviated pulmonary inflammation induced by AP. Blocking mtDNA oxidation or knocking down the TLR9/STING pathway effectively alleviated inflammation. Therefore, inhibition of JMJD3 or STING/TLR9 pathway blockage might be a potential therapeutic strategy to treat AP and the associated lung injury.

Phenotypic Heterogeneity Analysis of APC-Mutant Colon Cancer by Proteomics and Phosphoproteomics Identifies RAI14 as a Key Prognostic Determinant in East Asians and Westerners.

Adenomatous polyposis coli (APC) is an important tumor suppressor and is mostly linked to the regulation of the Wnt/ß-catenin signaling pathway. APC mutation has been identified as an early event in more than 80% of sporadic colorectal cancers (CRCs). Moreover, prognostic differences are observed in CRC patients with APC mutations. Although previous genomics studies have investigated the roles of concomitant gene mutations in determining the phenotypic heterogeneity of APC-mutant tumors, valuable prognostic determinants for APC-mutant CRC patients are still lacking. Based on the proteome and phosphoproteome data, we classified APC-mutant colon cancer patients and revealed genomic, proteomic, and phosphoproteomic heterogeneity in APC-mutant tumors. More importantly, we identified RAI14 as a key prognostic determinant for APC-mutant but not APC-wildtype colon cancer patients. The heterogeneity and the significance of prognostic biomarkers in APC-mutant tumors were further validated in the Clinical Proteomic Tumor Analysis Consortium (CPTAC) colon cancer cohort. In addition, we found that colon cancer patients with high expression of RAI14 were less responsive to chemotherapy. Knockdown of RAI14 in cell lines led to reduced cell migration and changes in epithelial-mesenchymal transition (EMT)-related markers. Mechanistically, knockdown of RAI14 remodeled the phosphoproteome associated with cell adhesion, which might affect EMT marker expression and promote F-actin degradation. Collectively, this work describes the phenotypic heterogeneity of APC-mutant tumors and identifies RAI14 as an important prognostic determinant for APC-mutant colon cancer patients. The prognostic utility of RAI14 in APC-mutant colon cancer will provide early warning and increase the chance of successful treatment.

Deciphering the Clinical Significance and Kinase Functions of GSK3α in Colon Cancer by Proteomics and Phosphoproteomics.

GSK3α and GSK3ß are two GSK3 isoforms with 84% overall identity and 98% identity in their catalytic domains. GSK3ß plays important roles in the pathogenesis of cancer, while GSK3α has long been considered a functionally redundant protein of GSK3ß. Few studies have specifically investigated the functions of GSK3α. In this study, unexpectedly, we found that the expression of GSK3α, but not GSK3ß, was significantly correlated with the overall survival of colon cancer patients in 4 independent cohorts. To decipher the roles of GSK3α in colon cancer, we profiled the phosphorylation substrates of GSK3α and uncovered 156 phosphosites from 130 proteins specifically regulated by GSK3α. A number of these GSK3α-mediated phosphosites have never been reported before or have been incorrectly identified as substrates of GSK3ß. Among them, the levels of HSF1S303p, CANXS583p, MCM2S41p, POGZS425p, SRRM2T983p, and PRPF4BS431p were significantly correlated with the overall survival of colon cancer patients. Further pull-down assays identified 23 proteins, such as THRAP3, BCLAF1, and STAU1, showing strong binding affinity to GSK3α. The interaction between THRAP3 and GSK3α was verified by biochemical experiments. Notably, among the 18 phosphosites of THRAP3, phosphorylation at S248, S253, and S682 is specifically mediated by GSK3α. Mutation of S248 to D (S248D), which mimics the effect of phosphorylation, obviously increased cancer cell migration and the binding affinity to proteins related to DNA damage repair. Collectively, this work not only discloses the specific function of GSK3α as a kinase but also suggests GSK3α as a promising therapeutic target for colon cancer.

Colorectal cancer liver metastasis: genomic evolution and crosstalk with the liver microenvironment.

Colorectal cancer (CRC) patients frequently develop liver metastases, which are the major cause of cancer-related mortality. The molecular basis and management of colorectal liver metastases (CRLMs) remain a challenging clinical issue. Recent genomic evidence has demonstrated the liver tropism of CRC and the presence of a stricter evolutionary bottleneck in the liver as a target organ compared to lymph nodes. This bottleneck challenging CRC cells in the liver is organ-specific and requires adaptation not only at the genetic level, but also at the phenotypic level to crosstalk with the hepatic microenvironment. Here, we highlight the emerging evidence on the clonal evolution of CRLM and review recent insights into the molecular mechanisms orchestrating the bidirectional interactions between metastatic CRC cells and the unique liver microenvironment.

Unveiling the hidden: identification and management of overlooked blood vessels in laparoscopic left hemicolectomy for splenic flexure cancer.

BACKGROUND: During laparoscopic left hemicolectomy procedures, a previously overlooked consistently thick blood vessel within the gastrocolic ligament near the splenic hilum may contribute to post-operative bleeding complications. The purpose of this study was to investigate the identification and management of the previously overlooked blood vessel. METHODS: This is a retrospective descriptive study of patients undergoing laparoscopic left colectomy for splenic fexure cancer conducted at a national gastrointestinal surgery centre in China. Consecutive patients with splenic fexure cancer who underwent laparoscopic left colectomy using our"five-step process"(n = 34) between January 2021 and July 2023 were included. RESULTS: The vessels can be effectively exposed using the aforementioned "five-step process." It was observed that the overlooked vessels consistently present in all patients were identified as the omental branch of the left gastroepiploic artery and vein. CONCLUSION: We have identified the origin of previously overlooked blood vessels and recommended a safe method for their management. This may offer advantages to colorectal surgeons performing laparoscopic left colectomy for splenic flexure cancer.

MRI-based deep learning model for differentiation of hepatic hemangioma and hepatoblastoma in early infancy.

Hepatic hemangioma (HH) and hepatoblastoma (HBL) are common pediatric liver tumors and present with similar clinical manifestations with limited distinguishing value of serum AFP in early infancy. An accurate differentiation diagnostic tool is warranted for optimizing treatments and improving prognosis. The present study aimed to develop an innovative and cost-effective diagnostic tool to differentiate HH and HBL in early infancy using advanced deep learning (DL) techniques. One hundred forty patients ≤4 months old diagnosed as HH or HBL with histological specimens were recruited from two institutions assigned into a training set with cross-validation and a testing set for external validation, respectively. Based on MRI images, imaging diagnoses were interpreted by two radiologists, and imaging-derived radiomic features were extracted by pretrained convolutional neural networks (CNNs)-Xception extractor via DL analysis. A nomogram model was constructed integrating predictive clinical variables, radiologist-based interpretation, and DL features, evaluated comprehensively on diagnostic and calibration accuracy. The DL-based model performed an area under the receiver operating characteristic curve (AUC) of 0.966 for the training cohort and 0.864 for the testing cohort. The radiologist-interpreted differentiation model showed an AUC of 0.837 in the testing cohort. The integrated nomogram model represented an increasing performance with an AUC of 0.887, accuracy of 78.57%, sensitivity of 76.19%, and specificity of 80.95% in the testing cohort. CONCLUSION:  The MRI-based integrated model, a noninvasive preoperative diagnostic tool, yielded favorable efficacy for differentiating HH and HBL in early infancy, which might reduce the patients' costs of repetitive and unnecessary examinations or over-treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05170282. WHAT IS KNOWN: • Hepatic hemangioma (HH) and hepatoblastoma (HBL) are common pediatric liver tumors and present with similar clinical manifestations with limited distinguishing value of serum AFP in early infancy. • Considering the rare incidence of infantile hepatic tumors, the distinguishing accuracy between HBL and HH for cases in early infancy is unsatisfactory for radiologists' recognition solely. WHAT IS NEW: • The MRI-based integrated model, a noninvasive preoperative diagnostic tool yielded favorable efficacy for differentiating HH and HBL in early infancy, which might reduce the patients' costs of repetitive and unnecessary examinations or over-treatment.

Age-Associated Proteomic Signatures and Potential Clinically Actionable Targets of Colorectal Cancer.

The occurrence and prevalence of colorectal cancer (CRC) is closely associated with age. More than 90% of patients with CRC are diagnosed after 50 years of age. However, CRC incidence of young individuals has been increasing since 1990s, whereas the overall CRC frequency is declining. Distinct overall survival rates between young and aged patients with CRC have been established. Tremendous efforts have been made to clarify the underlying mechanisms of age-dependent clinical differences, but it still remains elusive. Here, we performed proteomic profiling of 50 patients with CRC and revealed proteomic signatures of CRC across age groups. Gene set enrichment analysis showed that distinct age-dependent clinical outcomes might mainly attribute to varied MYC targets V1/V2, E2F targets and G2M checkpoint gene sets, which were associated with cancer cell proliferation, cell apoptosis, tumor growth, and tumor metastasis. Multiple linear regression analysis revealed a large number of functional proteins, such as NOP2, CSE1L, NHP2, NOC2L and CDK1, with adjusted expression significantly correlated with age (p < 0.05). Among them, NHP2 is a core component of the telomerase complex associated with age. High NHP2 expression predicted poor overall survival, with a more significant correlation in aged patients with CRC. Knockdown of NHP2 significantly suppressed cancer cell proliferation. In addition, we revealed some age-related potential clinically actionable targets, such as PSEN1, TSPO, and CDK1, which might be more suitable for patients with late-onset CRC. Collectively, this study identifies age-associated proteomic signatures and potential therapeutic targets of CRC and may help make a precise decision on CRC treatment.

Hypomethylation of GDNF family receptor alpha 1 promotes epithelial-mesenchymal transition and predicts metastasis of colorectal cancer.

Tumor metastasis is the major cause of poor prognosis and mortality in colorectal cancer (CRC). However, early diagnosis of highly metastatic CRC is currently difficult. In the present study, we screened for a novel biomarker, GDNF family receptor alpha 1 (GFRA1) based on the expression and methylation data in CRC patients from The Cancer Genome Altlas (TCGA), followed by further analysis of the correlation between the GFRA1 expression, methylation, and prognosis of patients. Our results show DNA hypomethylation-mediated upregulation of GFRA1 in invasive CRC, and it was found to be correlated with poor prognosis of CRC patients. Furthermore, GFRA1 methylation-modified sequences were found to have potential as methylation diagnostic markers of highly metastatic CRC. The targeted demethylation of GFRA1 by dCas9-TET1CD and gRNA promoted CRC metastasis in vivo and in vitro. Mechanistically, demethylation of GFRA1 induces epithelial-mesenchymal transition (EMT) by promoting AKT phosphorylation and increasing c-Jun expression in CRC cells. Collectively, our findings indicate that GFRA1 hypomethylation can promote CRC invasion via inducing EMT, and thus, GFRA1 methylation can be used as a biomarker for the early diagnosis of highly metastasis CRC.

[Construction and Exploration of Simulative Virtual Curriculum of Laparoscopy for Standardized Surgical Residency Training]. / å¤–ç§‘ä½é™¢åŒ»å¸ˆåŸ¹è®­çš„è ¹è ”é•œæ¨¡æ‹Ÿè™šæ‹Ÿè¯¾ç¨‹å»ºè®¾æŽ¢ç´¢.

Laparoscopic operations have become an indispensable therapeutic measure in surgical treatment due to the emerging trends of minimal invasiveness and precision in the field of surgery. Laparoscopic skills have gradually become part of the essential skills for young surgeons and hospitals at all levels are giving high priority to laparoscopic skills training. The innovation and development of simulative and virtual medical technology has given rise to effective ways and platforms for the training of laparoscopy surgeons in China. Based on the laparoscopy simulative virtual technology, our hospital gradually developed a systematic training and evaluation system for the laparoscopy training of surgical residents by offering theory courses on laparoscopy, conducting simulative and virtual systematic training, and developing assessment criteria for the training. Herein, we presented and shared our experience in applying laparoscopy simulative virtual technology in the training of surgical residents in order to promote the standardized residency training of laparoscopic skills in China and to provide reference for the implementation of standardized training of laparoscopic skills.

Genomic evolution and diverse models of systemic metastases in colorectal cancer.

OBJECTIVE: The systemic spread of colorectal cancer (CRC) is dominated by the portal system and exhibits diverse patterns of metastasis without systematical genomic investigation. Here, we evaluated the genomic evolution of CRC with multiorgan metastases using multiregion sequencing. DESIGN: Whole-exome sequencing was performed on multiple regions (n=74) of matched primary tumour, adjacent non-cancerous mucosa, liver metastasis and lung metastasis from six patients with CRC. Phylogenetic reconstruction and evolutionary analyses were used to investigate the metastatic seeding pattern and clonal origin. Recurrent driver gene mutations were analysed across patients and validated in two independent cohorts. Metastatic assays were performed to examine the effect of the novel driver gene on the malignant behaviour of CRC cells. RESULTS: Based on the migration patterns and clonal origins, three models were revealed (sequential, branch-off and diaspora), which not only supported the anatomic assumption that CRC cells spread to lung after clonally expanding in the liver, but also illustrated the direct seeding of extrahepatic metastases from primary tumours independently. Unlike other cancer types, polyphyletic seeding occurs in CRC, which may result in late metastases with intermetastatic driver gene heterogeneity. In cases with rapid dissemination, we found recurrent trunk loss-of-function mutations in ZFP36L2, which is enriched in metastatic CRC and associated with poor overall survival. CRISPR/Cas9-mediated knockout of ZFP36L2 enhances the metastatic potential of CRC cells. CONCLUSION: Our results provide genomic evidence for metastatic evolution and indicate that biopsy/sequencing of metastases may be considered for patients with CRC with multiorgan or late postoperative metastasis.

Noncoding RNAs in tumor metastasis: molecular and clinical perspectives.

Metastasis is the main culprit of cancer-associated mortality and involves a complex and multistage process termed the metastatic cascade, which requires tumor cells to detach from the primary site, intravasate, disseminate in the circulation, extravasate, adapt to the foreign microenvironment, and form organ-specific colonization. Each of these processes has been already studied extensively for molecular mechanisms focused mainly on protein-coding genes. Recently, increasing evidence is pointing towards RNAs without coding potential for proteins, referred to as non-coding RNAs, as regulators in shaping cellular activity. Since those first reports, the detection and characterization of non-coding RNA have explosively thrived and greatly enriched the understanding of the molecular regulatory networks in metastasis. Moreover, a comprehensive description of ncRNA dysregulation will provide new insights into novel tools for the early detection and treatment of metastatic cancer. In this review, we focus on discussion of the emerging role of ncRNAs in governing cancer metastasis and describe step by step how ncRNAs impinge on cancer metastasis. In particular, we highlight the diagnostic and therapeutic applications of ncRNAs in metastatic cancer.

Endoscopic stent versus diverting stoma as a bridge to surgery for obstructive colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Self-expandable metallic stent (SEMS), an alternative to diverting stoma (DS), has been used as a "bridge to surgery" (BTS) to decompress acute obstruction of colorectal cancer (CRC) for decades. However, whether SEMS is a safe technique for obstruction of CRC without compromising the long-term survival of patients remains unidentified compared to those of DS. The aim of the present study was to elucidate the safety and survival outcomes of SEMS and DS. METHODS: Embase, PubMed, and Medline were searched for qualified studies published until October, 2020, in which SEMS or DS was performed as a BTS without resection at the same stage. The last search was on December 5th, 2020. The Newcastle-Ottawa scale (NOS) was used to assess the quality of included studies. The major complication rate, mortality, 3-year overall survival (OS), and permanent stoma rate were estimated as outcomes. RESULTS: The present study was registered on INPLASY (No. 2020100079). Seven eligible studies were included, involving 646 and 712 patients who underwent SEMS and DS treatments, respectively. The Clavien-Dindo I/II grade complication rate was significantly lower in the SEMS group than in the DS group (8.68 vs. 16.85%; RR, 0.59; 95% confidence interval (CI) 0.41-0.84; P = 0.004). The Clavien-Dindo III/IV grade complication rate was comparable in two groups (7.69 vs. 8.79%; RR, 0.82; 95% CI 0.54-1.27; P = 0.37). There were no statistical differences in the short-term mortality (5.16 vs. 4.53%; RR, 1.25; 95% CI 0.75-2.08; P = 0.39), 3-year OS (71.91 vs. 76.60%; RR, 0.93; 95% CI 0.86-1.01; P = 0.10), and permanent stoma rate (22.08 vs. 27.54%; RR, 0.84; 95% CI 0.67-1.06; P = 0.14) between the two groups. CONCLUSIONS: To some extent, SEMS is a safe BTS technique for acute obstructive CRC, without significant adverse effect on the survival of patients. Given the advantage of minimal invasion, SEMS may be a better alternative to DS for obstructive CRC. However, the conclusions remain to be discussed because of lacking high-quality randomized controlled trails.

PDLIM1 Inhibits Tumor Metastasis Through Activating Hippo Signaling in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Tumor metastasis is a major factor of high recurrence and mortality in hepatocellular carcinoma (HCC), but its underlying mechanism remains elusive. We report that PDZ and LIM domain protein 1 (PDLIM1) is significantly down-regulated in metastatic human HCC tissues, which predicts unfavorable prognosis, suggesting that PDLIM1 may play an important inhibitory role during HCC metastasis. APPROACH AND RESULTS: Functional studies indicate that PDLIM1 knockdown induces epithelial-to-mesenchymal transition (EMT) of HCC cells, elevates their invasive capacity, and promotes metastasis in vitro and in vivo, whereas overexpression of PDLIM1 exhibits opposite phenotypes. Mechanistically, PDLIM1 competitively binds to the cytoskeleton cross-linking protein alpha-actinin 4 (ACTN4), leading to the disassociation of ACTN4 from F-actin, thus preventing F-actin overgrowth. In contrast, loss of PDLIM1 induces excessive F-actin formation, resulting in dephosphorylation of large tumor suppressor kinase 1 and activation of Yes-associated protein, thereby promoting HCC metastasis. Moreover, Asn145 (N145) of PDLIM1 is critical for its interaction with ACTN4, and N145A mutation abolishes its regulatory function in Hippo signaling and HCC metastasis. CONCLUSIONS: Our findings indicate that PDLIM1 suppresses HCC metastasis by modulating Hippo signaling, suggesting that PDLIM1 may be a potential prognostic marker for metastatic HCC.

The bromodomain and extra-terminal domain inhibitor JQ1 synergistically sensitizes human colorectal cancer cells to topoisomerase I inhibitors through repression of Mre11-mediated DNA repair pathway.

Camptothecin (CPT) and its derivatives, irinotecan and topotecan are specific topoisomerase I (Top1) inhibitors and potent anticancer drugs. Mechanistically, they induce DNA double-strand breaks (DSBs). Although CPT is an effective chemotherapeutic agent used in the management of advanced colorectal cancer, there exist associated side effects. Herein, we aimed to establish novel drug combinations that can effectively aid in managing the CPT-related side effects. Besides, bromodomain and extra-terminal domain (BET) inhibitors have proved as promising drugs that target epigenetic mechanisms in various cancers, they alter DNA repair processes, hence are a potential candidate for CPT synthetic lethality. A novel BET inhibitor JQ1 synergized with CPT, exerted antiproliferative effects. Through cell cycle analyses and apoptosis assays, we revealed that a combination of CPT and JQ1 induces subG1-phase arrest and enhances cell apoptosis. This combination increased the intensity of γ-H2AX staining, a specific marker of DSBs. Moreover, colorectal cancer cells highly expressing Top1 showed greater sensitivity to JQ1, which was lowered through the lentiviral shRNA-mediated knockdown of Top1. JQ1, combined with CPT, impeded the recruitment of the Mre11-mediated MRN complex. Finally, JQ1 enhanced the in vivo sensitivity of tumors to CPT without inducing toxicity. These results demonstrate that a combination of BET inhibitor with Top1 inhibitor is safe and exerts positive chemotherapeutic effects in colorectal cancer.

The long-term survival outcomes of gastric cancer patients with total intravenous anesthesia or inhalation anesthesia: a single-center retrospective cohort study.

BACKGROUND: The relationship between the type of anesthesia and the survival outcomes of gastric cancer patients is uncertain. This study compared the overall outcome of gastric cancer patients after surgery with total intravenous anesthesia (TIVA) or inhalation anesthesia (IHA). METHODS: Clinicopathological variables of gastric cancer patients were retrieved from the database of the Surgical Gastric Cancer Patient Registry in West China Hospital, Sichuan University. Patients were grouped according to whether they received TIVA or IHA during the operation. Propensity score (PS) matching was used to balance the baseline variables, and survival outcomes were compared between these two groups. In addition, studies comparing survival outcomes between TIVA and IHA used for gastric cancer surgery and published before April 20th, 2020, were identified, and their data were pooled. RESULTS: A total of 2827 patients who underwent surgical treatment from Jan 2009 to Dec 2016 were included. There were 323 patients in the TIVA group and 645 patients in the IHA group, with 1:2 PS matching. There was no significant difference in overall survival outcomes between the TIVA and IHA groups before matching the cohort (p = 0.566) or after matching the cohort (p = 0.679) by log-rank tests. In the Cox hazard regression model, there was no significant difference between the TIVA and IHA groups before (HR: 1.054, 95% CI: 0.881-1.262, p = 0.566) or after (HR: 0.957, 95% CI: 0.779-1.177, p = 0.679) PS matching. The meta-analysis of survival outcomes between the TIVA and IHA groups found critical statistical value in the before PS matching cohort (HR 0.74, 95% CI: 0.57-0.96 p < 0.01) and after PS matching cohort (HR: 0.65, 95% CI: 0.46-0.94, p < 0.01). CONCLUSIONS: Combined with the results of previous studies, total intravenous anesthesia has been shown to be superior to inhalation anesthesia in terms of overall survival for gastric cancer patients undergoing surgical treatment. The selection of intravenous or inhalation anesthesia for gastric cancer surgery should take into account the long-term prognosis of the patient.

Effects of Adjuvant Therapy Compliance and Anastomotic Leakage on the Oncologic Outcomes of Patients With Rectal Cancer After Curative Resection.

BACKGROUND: Anastomotic leakage might be directly or indirectly related to the prognosis of patients with rectal cancer. OBJECTIVE: This study aimed to investigate whether anastomotic leakage affects the oncologic outcomes in patients with rectal cancer. DESIGN: This was a retrospective analysis of prospectively collected data. SETTINGS: This study was conducted at a teaching hospital between January 2009 and December 2013. PATIENTS: Patients who underwent curative resection for primary rectal cancer were included. MAIN OUTCOME AND MEASURE: Kaplan-Meier analyses were used to evaluate disease-free survival and overall survival. RESULTS: The overall incidence of anastomotic leakage was 2.7% (107/3865). Local recurrence was more frequent in patients with anastomotic leakage than in those without (14.0% vs 6.7%; p = 0.007). By multivariate analysis, anastomotic leakage was associated with increased local recurrence rate (p = 0.014) and poorer overall survival (p = 0.011). In subgroup analysis, compared with other pathologic risk factors, anastomotic leakage was associated with higher occurrence of local and distant recurrence in patients with stage II rectal cancer (p = 0.031 and <0.001). In patients with stage III rectal cancers, adjuvant therapy was more likely to be delayed or canceled in those experiencing anastomotic leakage (63 vs 39 d, p < 0.001; 37.3% vs 66.7%, p < 0.001). In addition, this patient group had the worst survival outcome when compared with those without anastomotic leakage and those with timely adjuvant therapy (5-year disease-free survival rate, p = 0.013; 5-year overall survival rate, p = 0.001). LIMITATIONS: This study is limited by its retrospective nature. CONCLUSIONS: There was a robust association between anastomotic leakage and local recurrence, while also potentially affect long-term survival of the patient group. Delayed or cancelled adjuvant therapy administration because of anastomotic leakage may partly account for the poorer survival in those patients with advanced rectal cancer. See Video Abstract at http://links.lww.com/DCR/B459. EFECTOS DE OBSERVANCIA DE TERAPIA ADYUVANTE Y FUGA ANASTOMTICA, EN RESULTADOS ONCOLGICOS DE PACIENTES CON CNCER RECTAL, DESPUS DE UNA RESECCIN CURATIVA: ANTECEDENTES:La fuga anastomótica podría estar relacionada directa o indirectamente, con el pronóstico de los pacientes con cáncer de recto.OBJETIVO:El estudio tuvo como objetivo investigar si la fuga anastomótica afecta los resultados oncológicos, en pacientes con cáncer de recto.DISEÑO:Fue un análisis retrospectivo de datos recolectados prospectivamente.AJUSTE:El estudio se realizó en un hospital universitario entre enero de 2009 y diciembre de 2013.PACIENTES:Pacientes sometidos a resección curativa por cáncer rectal primario.PRINCIPALES MEDIDAS DE RESULTADO:Se utilizaron análisis de Kaplan-Meier para evaluar la supervivencia libre de enfermedad y supervivencia general.RESULTADOS:La incidencia global de fuga anastomótica fue del 2,7% (107/3865). La recurrencia local fue más frecuente en pacientes con fuga anastomótica, que en aquellos sin ella (14,0% frente a 6,7%, p = 0,007). Por análisis multivariado, la fuga anastomótica se asoció con una mayor tasa de recurrencia local (p = 0,014) y una peor supervivencia general (p = 0,011). En el análisis de subgrupos, en comparación con otros factores de riesgo patológicos, la fuga anastomótica se asoció con una mayor incidencia de recidiva local y a distancia en pacientes con cáncer rectal en estadio II (p = 0,031 y <0,001, respectivamente). En pacientes con cáncer rectal estadio III, la terapia adyuvante tuvo más probabilidades de retrasarse o cancelarse en aquellos que sufrían fuga anastomótica (63 vs 39 días, p <0,001; 37,3% vs 66,7%, p <0,001). Y este grupo de pacientes tuvo el peor resultado de supervivencia en comparación con aquellos sin fuga anastomótica y aquellos con terapia adyuvante oportuna (tasa de supervivencia libre de enfermedad a 5 años, p = 0,013; tasa de supervivencia global a 5 años, p = 0,001).LIMITACIONES:El estudio está limitado por su naturaleza retrospectiva.CONCLUSIONES:Hubo una sólida asociación entre la fuga anastomótica y la recurrencia local, mientras que también afecta potencialmente la supervivencia a largo plazo, del grupo de pacientes. La administración de terapia adyuvante retrasada o cancelada debido a una fuga anastomótica, puede explicar en parte, la menor supervivencia en aquellos pacientes con cáncer rectal avanzado. Consulte Video Resumen en http://links.lww.com/DCR/B459.

Nomograms for predicting cancer-specific and overall survival in patients with invasive extramammary Paget's disease.

Aim: To develop nomograms for predicting cancer-specific survival (CSS) and overall survival (OS) in patients with invasive extramammary Paget's disease (iEMPD). Patients & methods: Retrospective data of 1955 patients with iEMPD were collected from the Surveillance, Epidemiology, and End Results database. Nomograms for predicting CSS and OS were established using competing risk regression and Cox regression, respectively, and were internally validated. Results: Five (age, surgery, tumor location, stage and concurrent malignancy) and eight (gender, age, race, marital status, surgery, tumor location, stage and lymph node metastasis) clinicopathological factors were utilized to construct nomograms for predicting CSS and OS, respectively. The concordance indices of the nomograms for predicting CSS and OS were 0.78 and 0.73, respectively. The validation of the nomograms showed good calibration and discrimination. The decision curve analyses confirmed the clinical utility of these nomograms. Conclusion: The nomograms can be a reliable tool for treatment design and prognostic evaluation of iEMPD.

Lay abstract Invasive extramammary Paget's disease (iEMPD) is a rare type of cutaneous malignancy with a heterogeneous prognosis. The prognostic factors remain poorly described, resulting in unclear risk stratification of the patients with iEMPD. The purpose of this study is to identify the prognostic factors associated with cancer-specific and overall survival rates in iEMPD and to develop accurate risk stratification models to guide the design of individualized treatment regimens. Clinicopathological data of 1955 patients pathologically diagnosed with iEMPD were retrospectively collected from the Surveillance, Epidemiology, and End Results database, and were utilized for analysis and construction of models for predicting the long-term survival in patients with iEMPD. Eventually, five (age, surgery, tumor location, stage and concurrent malignancy) and eight (gender, age, race, marital status, surgery, tumor location, stage and lymph node metastasis) factors were chosen to develop models for predicting cancer-specific and overall survival, respectively. The prediction accuracy and clinical utility of the established models were confirmed in subsequent evaluation. Because iEMPD is an extremely rare disease that a lot of clinical practitioners might not be familiar with, the availability of these quantifiable predictive models will provide convenience in daily practice.

Application of clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area, a propensity score matching study and comparison with open gastrectomy.

BACKGROUND: Suprapancreatic lymphadenectomy is the essence of D2 radical gastric cancer surgery. The present study aimed to describe clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area. METHODS: The data from gastric cancer patients who underwent surgical treatment from September 2016 to December 2018 were collected. Patients were divided into clockwise modularized lymphadenectomy (CML) and traditional open gastrectomy (OG) groups according to the surgical treatment strategy. The propensity score matching method was utilized to balance the baseline characteristics between the two groups. RESULTS: Finally, 551 gastric cancer patients were included in the present study. Following propensity score matching, 106 pairs of patients in the CML group and OG group were included in the final analysis. The CML group had more total examined lymph nodes (36, IQR 28-44.74 vs. 29, IQR 29-39.5, p = 0.002) and no. 9 station nodes (2, IQR 1-5 vs. 2, IQR 1-3, p = 0.007) than the OG group. There was less intraoperative blood loss (30, IQR 20-80 ml vs. 80, IQR 50-80 ml, p < 0.001) and a longer surgical duration (262.5 min, IQR 220-303.25 min vs. 232, IQR 220-255 min, p < 0.001) in the CML group than in the OG group. The incidence of postoperative complications (19.8% vs. 16.0%, p = 0.591) and postoperative hospital stay (8, IQR 7-9 days vs. 8, IQR 7-9 days, p = 0.452) were comparable between the CML and OG groups. CONCLUSION: Laparoscopic lymphadenectomy for gastric cancer surgery is technically demanding. Clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area can attain similar effects as traditional open surgery and without an increase in postoperative adverse events.

Closure of Petersen's defect in gastrectomy for gastric cancer: an interrupted time series analysis from a high-volume institution in China.

PURPOSE: Petersen's hernia (PH) is a serious complication after gastrectomy for gastric cancer. The aim of this study was to investigate whether closure of Petersen's defect (PD) can decrease the rates of PH and suspected Petersen's hernia (SPH). METHODS: Patients who underwent gastrectomy with PD were enrolled. From January 2014 to January 2017, we performed gastrectomy without PD closure (non-closure group). From February 2017 to June 2018, we closed PDs during gastrectomy (closure group). The rates of PH and SPH were compared between the two groups. The last follow-up was updated in August 2020. RESULTS: Among a total of 1213 patients, 12 patients (1.0%) developed PH, and 23 patients (1.9%) developed SPH. The rate of PH in the closure group was significantly lower than that in the non-closure group (1/385, 0.3% versus 11/828, 1.3%, p = 0.042, log-rank test). The rate of SPH in the closure group was significantly lower than that in the non-closure group (1/385, 0.3% versus 22/828, 2.7%, p = 0.008, log-rank test). Non-closure of PD was a risk factor for PH and SPH (odds ratio (OR) 7.72, 95% CI 1.84-32.35, p = 0.006). CONCLUSIONS: PD closure is recommended after gastrectomy for gastric cancer, as the rates of PH and SPH were significantly decreased.