Feasibility, Indications, and Prognostic Significance of Selective Lateral Pelvic Lymph Node Dissection After Preoperative Chemoradiotherapy in Middle/Low Rectal Cancer: Results of a Multicenter Lateral Node Study in China.

BACKGROUND: Lateral pelvic lymph node dissection after preoperative chemoradiotherapy can decrease local recurrence to lateral compartments, thereby providing survival benefits. OBJECTIVE: The safety of lateral pelvic lymph node dissection after preoperative chemoradiotherapy was investigated, and the surgical indications and survival benefits of lateral pelvic lymph node dissection were established on the basis of preoperative characteristics. DESIGN: A multicenter retrospective study. SETTINGS: Three hospitals in China. PATIENTS: Four hundred nine patients with clinical evidence of lateral pelvic lymph node metastasis. INTERVENTIONS: Patients who received lateral pelvic lymph node dissection were divided into 2 groups depending on whether they received chemoradiotherapy (n = 139) or not (n = 270). MAIN OUTCOME MEASURES: The safety, indications, and survival benefits of lateral pelvic lymph node dissection after preoperative chemoradiotherapy were investigated. RESULTS: The surgery times were significantly prolonged by preoperative chemoradiotherapy (291.3 vs 265.5 min; p = 0.021). Multivariate analysis demonstrated that poor/mucinous/signet-ring adenocarcinoma (OR = 4.42, 95% CI, 2.24-11.27; p = 0.031) and postchemoradiotherapy lateral pelvic lymph node short-axis diameter ≥7 mm (OR = 15.2, 95% CI, 5.89-53.01; p < 0.001) were independent predictive factors for lateral pelvic lymph node metastasis. Multivariate prognostic analysis showed that swollen lateral pelvic lymph nodes beyond the obturator or internal iliac as well as the involvement of 3 or more lateral pelvic lymph nodes were independent adverse prognostic factors. LIMITATIONS: The retrospective nature of the study and the small sample size were the limitations of this study. CONCLUSIONS: Preoperative chemoradiotherapy combined with lateral pelvic lymph node dissection is a practicable procedure with acceptable morbidity. Postchemoradiotherapy lateral pelvic lymph node short-axis diameter ≥7 mm and poor/signet/mucinous adenocarcinoma could be used for predicting lateral pelvic lymph node metastasis after chemoradiotherapy. However, lateral pelvic lymph node dissection should be carefully considered in patients with swollen lateral pelvic lymph nodes beyond the obturator or internal iliac region or involvement of multiple lateral pelvic lymph nodes. See Video Abstract at http://links.lww.com/DCR/C133 . VIABILIDAD, INDICACIONES E IMPORTANCIA PRONSTICA DE LA DISECCIN SELECTIVA DE GANGLIOS LINFTICOS PLVICOS LATERALES DESPUS DE QUIMIORRADIOTERAPIA PREOPERATORIA EN CNCER DE RECTO MEDIO/INFERIOR RESULTADOS DE UN ESTUDIO MULTICNTRICO DE GANGLIOS LATERALES EN CHINA: ANTECEDENTES:La disección de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia preoperatoria puede disminuir la recurrencia local en los compartimentos laterales, lo que brinda beneficios de supervivencia.OBJETIVO:Se investigó la seguridad de la disección de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia preoperatoria, y se establecieron las indicaciones quirúrgicas y los beneficios de supervivencia de la disección de los ganglios linfáticos pélvicos laterales en función de las características preoperatorias.DISEÑO:Estudio retrospectivo multicéntrico.ESCENARIO:Tres hospitales en China.PACIENTES:Cuatrocientos nueve pacientes con evidencia clínica de metástasis en los ganglios linfáticos pélvicos laterales.INTERVENCIONES:Los pacientes que recibieron disección de ganglios linfáticos pélvicos laterales se dividieron en dos grupos dependiendo de si recibieron quimiorradioterapia (n = 139) o no (n = 270).PRINCIPALES MEDIDAS DE RESULTADO:Se investigaron la seguridad, las indicaciones y los beneficios de supervivencia de la disección de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia preoperatoria.RESULTADOS:Los tiempos de cirugía se prolongaron significativamente con la quimiorradioterapia preoperatoria (291,3 vs 265,5 min, p = 0,021). El análisis multivariable demostró que el adenocarcinoma mal diferenciado/mucinoso/en anillo de sello (odds ratio = 4,42, intervalo de confianza del 95%, 2,24-11,27; p = 0,031) y el diámetro del eje corto de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia ≥7 mm (odds ratio = 15,2, intervalo de confianza del 95%, 5,89-53,01; p < 0,001) fueron factores predictivos independientes de metástasis en los ganglios linfáticos pélvicos laterales. El análisis pronóstico multivariable mostró que la inflamación de los ganglios linfáticos pélvicos laterales más allá del obturador o la ilíaca interna, así como la afectación de tres o más ganglios linfáticos pélvicos laterales, eran factores pronósticos adversos independientes.LIMITACIONES:La naturaleza retrospectiva del estudio y el pequeño tamaño de la muestra.CONCLUSIONES:La quimiorradioterapia preoperatoria combinada con la disección de los ganglios linfáticos pélvicos laterales es un procedimiento practicable con una morbilidad aceptable. Posterior a la quimiorradioterapia, el diámetro del eje corto de los ganglios linfáticos pélvicos laterales ≥7 mm y el adenocarcinoma pobre/en sello/mucinoso podrían usarse para predecir la metástasis en los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia. Sin embargo, la disección de los ganglios linfáticos pélvicos laterales debe considerarse cuidadosamente en pacientes con ganglios linfáticos pélvicos laterales inflamados más allá del obturador o de la región ilíaca interna o compromiso de múltiples ganglios linfáticos pélvicos laterales. Consulte Video Resumen en http://links.lww.com/DCR/C133 . (Traducción-Dr. Felipe Bellolio ).

Applications of Near-Infrared Fluorescence Imaging and Angiography of Inferior Vesical Artery in Laparoscopic Lateral Lymph Node Dissection: A Prospective Nonrandomized Controlled Study.

BACKGROUND: Near-infrared imaging with indocyanine green has been used to guide lateral lymph node dissection, yet its efficacy and benefits need further investigation. OBJECTIVE: To investigate the efficacy and feasibility of near-infrared fluorescence imaging and angiography of the inferior vesical artery in laparoscopic lateral lymph node dissection. DESIGN: A prospective nonrandomized controlled study. SETTINGS: Single-center study. PATIENTS: Patients with lower rectal cancer who underwent total mesorectal excision plus lateral lymph node dissection. MAIN OUTCOME MEASURES: A cohort of 108 patients was enrolled. After propensity score matching, 29 patients in the near-infrared group and 50 patients in the non-near-infrared group were matched. The total number of harvested lateral lymph nodes, positive lateral lymph nodes, inferior vesical artery preservation, and postoperative urinary function were compared. RESULTS: After propensity score matching, both groups had similar baseline characteristics. The total number of harvested lateral lymph nodes in the near-infrared group was significantly higher (12 vs 9, p = 0.013), but positive lateral lymph nodes were similar between the 2 groups (1 vs 1, p = 0.439). The inferior vesical artery preservation ratio was significantly increased with the aid of indocyanine green angiography (93.1% vs 56.0%, p < 0.001). The non-near-infrared group required more days for urinary catheter removal than the near-infrared group (5 vs 4, p = 0.046). Urinary recatheterization tended to occur more frequently in the non-near-infrared group, with a marginally significant trend (16% vs 0%, p = 0.059). The non-near-infrared group tended to have more cases with residual urine volume ≥50 mL than the near-infrared group (20.0% vs 3.4%, p = 0.087), especially in the bilateral dissection subgroup (41.2% vs 0%, p = 0.041). LIMITATIONS: Small sample size. CONCLUSIONS: Near-infrared imaging increased the number of harvested lateral lymph nodes, whereas real-time indocyanine green fluorescence angiography ensured the preservation of the inferior vesical artery and tended to improve postoperative urinary function.

Matrix stiffness-mediated tenogenesis of tendon stem/progenitor cells via integrin-αm for tendon regeneration.

Tendon injuries, commonly associated with sports activities, pose significant challenges in terms of treatment and recovery due to limited tendon regeneration and the formation of proliferative scars. Stem cell-based therapy has shown promising application, but there are still challenges. Physical and biological cues are instrumental in guiding stem cell differentiation and maturation. This study focuses on exploring the effects of matrix biomechanics on tendon stem/progenitor cells (TSPCs) differentiation. We fabricated polydimethylsiloxane (PDMS) substrates with different elastic modulus to mimic the mechanical characteristics of healthy tendons. A tissue-engineered culture system was developed for tenogenesis, and pre-differentiated tissue-engineered tendons were transplanted in vivo to assess their efficacy in regenerating patella tendon injuries. Furthermore, we demonstrated that the biomechanical stimuli activated the integrin-αm to enhance the tenogenesis capacity of TSPCs. Our findings highlight the importance of biomechanics in tendon tissue engineering and provide a novel perspective for enhancing tendon regeneration.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Young Patients With Peritoneal Metastasis of Colorectal Cancer-An Asian Experience.

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are accepted treatment options for patients with cancers associated with the abdominal region. Currently, there are insufficient data that evaluate the effectiveness of these therapeutic options in young patients who have peritoneal metastasis (PM) originating from colorectal cancer. METHODS: In this investigation, we evaluated perioperative data, clinicopathological manifestations, and survival consequences in 46 younger (≤50 y) patients who underwent CRS and HIPEC therapy between 2017 June and 2019 June and then compared these data with 94 older patients (aged >50 y). RESULTS: Compared with older patients, younger patients had a higher synchronous PM incidence (78.3% versus 51.1%, P < 0.001) and were more likely to exhibit signet ring histology and mucinous (29.8% versus 60.9%; P < 0.001). The cancer-specific survival rates after CRS and HIPEC treatment were similar in both age sets. Multivariate Cox regression revealed that mucinous/signet adenocarcinoma (hazard ratio 2.20, 95% confidence interval 1.02-4.74; P = 0.044) and rectal origin (hazard ratio 2.51, 95% confidence interval 1.11-5.67; P = 0.027) were independent risk factors for a lower cancer-specific survival rate. CONCLUSIONS: Younger (age ≤50 y) patients who have PM of colorectal cancer origin often present synchronous PM, which is less commonly observed in older patients. Tumors in younger patients are more aggressive; however, post-CRS and HIPEC treatment, the benefits are similar to those observed in older cohorts.

Approach to Access Benzo[j]phenanthridinones from 1,7-Enynes and Aryldiazonium Salts via a Domino Radical Relay Process Enabled by a P/N-Heteroleptic Cu(I)-Photosensitizer.

A mild approach for the synthesis of benzo[j]phenanthridin-6(5H)-one derivatives from 1,7-enynes and aryldiazonium salts has been successfully developed involving a domino radical relay process enabled by a heteroleptic Cu(I)-photosensitizer under visible-light-driven photocatalytic conditions. Mechanistic studies disclosed that the oxidative quenching of the excited state of PS 4 with aryldiazonium salts via an SET process generated aryl radicals, which could play a radical initiator-terminator dual role within the whole radical relay process, namely, at the initial step acting as a radical donor to trigger the radical addition to the olefin moieties of 1,7-enynes while at the final stage serving as a radical acceptor to complete the cyclization.

Mesorectal excision with or without lateral lymph node dissection for elderly patients with mid-low rectal cancer: safety and feasibility analysis.

OBJECTIVE: The perioperative safety and survival benefits of lateral lymph node dissection in elderly patients have been less reported. This study aimed to compare short-term and survival outcomes of total mesorectal excision and total mesorectal excision + lateral lymph node dissection in elderly patients. METHODS: A total of 444 elderly patients (≥65 years) with middle-low rectal cancer were enrolled in three institutions and divided into the total mesorectal excision + lateral lymph node dissection group (n = 110) and the total mesorectal excision group (n = 334). Eighty-three matched pairs were selected for evaluation after propensity matching. Data of 297 patients (age <65 years) with middle-low rectal cancer who underwent total mesorectal excision + lateral lymph node dissection were also collected and reviewed. Clinical and pathological features, postoperative outcomes and survival data were collected and analyzed. RESULTS: Compared with the total mesorectal excision group, the operation time of patients in the total mesorectal excision + lateral lymph node dissection group was significantly longer (277.6 vs. 171.4 min, P < 0.001), and the estimated blood loss was significantly more (119.6 vs. 57.5 ml, P = 0.014). Although there was no significant difference in overall complications (24.1% vs. 14.4%, P = 0.115) and grade 3-5 complications (9.6% vs. 7.2%, P = 0.576) between the two groups, the incidence of urinary retention (10.8% vs. 2.4%, P = 0.029) was higher in the total mesorectal excision + lateral lymph node dissection group. Two groups of patients achieve a similar 3-year overall survival (92.8% vs. 85.4%, P = 0.195) and 3-year disease-free survival (81.5% vs. 73.0%, P = 0.625). In addition, we compared long-term outcomes in 110 elderly patients with total mesorectal excision + lateral lymph node dissection and 297 non-elderly patients with total mesorectal excision + lateral lymph node dissection, and the results showed that 3-year (89.2% vs. 80.9%, P = 0.546) and disease-free survival (76.4% vs. 70.4%, P = 0.346) were similar between elderly and non-elderly patients. CONCLUSIONS: Although urinary retention is closely related to the implementation of lateral lymph node dissection in elderly patients, total mesorectal excision with lateral lymph node dissection could be performed safely with accepted overall and grade 3-5 postoperative complications in elderly patients with rectal cancer. Moreover, elderly patients with clinical lateral lymph node metastasis can also benefit from lateral lymph node dissection as well as younger patients. Prospective studies with large sample sizes are needed to verify our results further.

Surgical outcomes of left hemicolon sparing resection versus extensive resection in treating synchronous colorectal cancer involving the right-sided colon and sigmoid colon or rectum.

BACKGROUND: There are different surgical strategies that can treat synchronous colorectal cancer (SCRC) involving separate segments, namely extensive resection (EXT) and left hemicolon-sparing resection (LHS). We aim to comparatively analyze short-term surgical results, bowel function, and long-term oncological outcomes between SCRC patients treated with the two different surgical strategies. METHODS: One hundred thirty-eight patients with SCRC lesions located in the right hemicolon and rectum or sigmoid colon were collected at the Cancer Hospital, Chinese Academy of Medical Sciences, and the Peking University First Hospital from January 2010 to August 2021 and divided into EXT group (n = 35) and LHS group (n = 103), depending on their surgical strategies. These two groups of patients were compared for postoperative complications, bowel function, the incidence of metachronous cancers, and prognosis. RESULTS: The operative time for the LHS group was markedly shorter compared with the EXT group (268.6 vs. 316.9 min, P = 0.015). The post-surgery incidences of total Clavien-Dindo grade ≥ II complications and anastomotic leakage (AL) were 8.7 vs. 11.4% (P = 0.892) and 4.9 vs. 5.7% (P = 1.000) for the LHS and EXT groups, respectively. The mean number of daily bowel movements was significantly lower for the LHS group than for the EXT group (1.3 vs. 3.8, P < 0.001). The proportions of no low anterior resection syndrome (LARS), minor LARS, and major LARS for the LHS and EXT groups were 86.5 vs. 80.0%, 9.6 vs. 0%, and 3.8 vs. 20.0%, respectively (P = 0.037). No metachronous cancer was found in the residual left colon during the 51-month (median duration) follow-up period. The overall and disease-free survival rates at 5 years were 78.8% and 77.5% for the LHS group and 81.7% and 78.6% for the EXT group (P = 0.565, P = 0.712), respectively. Multivariate analysis further confirmed N stage, but not surgical strategy, as the risk factor that independently affected the patients' survival. CONCLUSIONS: LHS appears to be a more appropriate surgical strategy for SCRC involving separate segments because it exhibited shorter operative time, no increase in the risk of AL and metachronous cancer, and no adverse long-term survival outcomes. More importantly, it could better retain bowel function and tended to reduce the severity of LARS and therefore improve the post-surgery life quality of SCRC patients.

Prognostic value of consolidation-to-tumor ratio on computed tomography in NSCLC: a meta-analysis.

BACKGROUND: Although several studies have confirmed the prognostic value of the consolidation to tumor ratio (CTR) in non-small cell lung cancer (NSCLC), there still remains controversial about it. METHODS: We systematically searched the PubMed, Embase, and Web of Science databases from inception to April, 2022 for eligible studies that reported the correlation between CTR and prognosis in NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and pooled to assess the overall effects. Heterogeneity was estimated by I2 statistics. Subgroup analysis based on the cut-off value of CTR, country, source of HR and histology type was conducted to detect the sources of heterogeneity. Statistical analyses were performed using STATA version 12.0. RESULTS: A total of 29 studies published between 2001 and 2022 with 10,347 patients were enrolled. The pooled results demonstrated that elevated CTR was associated with poorer overall survival (HR = 1.88, 95% CI 1.42-2.50, P < 0.01) and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS) (HR = 1.42, 95% CI 1.27-1.59, P < 0.01) in NSCLC. According to subgroup analysis by the cut-off value of CTR and histology type, both lung adenocarcinoma and NSCLC patients who had a higher CTR showed worse survival. Subgroup analysis stratified by country revealed that CTR was a prognostic factor for OS and DFS/RFS/PFS in Chinese, Japanese, and Turkish patients. CONCLUSIONS: In NSCLC patients with high CTR, the prognosis was worse than that with low CTR, indicating that CTR may be a prognostic factor.

Feasibility and safety of lateral pelvic lymph node dissection for elderly patients with middle-low rectal cancer: results of a large multicenter lateral node collaborative group study in China.

BACKGROUND: Lateral pelvic lymph node (LPN) dissection can improve local control in certain rectal cancer patients with LPN metastasis. However, the effects of this technically complex procedure on perioperative safety and long-term survival of elderly patients (≥ 70 years) remain unclear. METHODS: Locally advanced middle-low rectal cancer patients diagnosed with LPN metastasis who underwent total mesorectal excision (TME) with LPN dissection at three institutions from January 2012 to December 2019 were included in this study. Additionally patients who had neoadjuvant chemoradiotherapy (nCRT) and those who did not were compared. RESULTS: In total there were 407 patients, including 49 elderly and 358 non-elderly patients, of which 249 were male, with a median age of 58 years (range:18-85 years). In the whole cohort, operation time (280.7 vs. 292.0 min, p = 0.498) and estimated blood loss (100 vs. 100 ml, p = 0.384) were comparable in the elderly and non-elderly groups. There was no significant difference in the incidences of overall complications (24.5% vs. 19.8%, p = 0.448) and severe (Clavien-Dindo grade 3-5) surgical complications (8.2% vs. 7.5%, p = 0.778) between the two groups. However, the incidence of urinary retention (14.3% vs. 5.6%, p = 0.032) and intensive care unit admission (16.3% vs. 6.1%, p = 0.018) was significantly higher in the elderly group compared with those in the non-elderly group. The 3-year overall survival (88.7% vs. 82.1%, p = 0.516) and disease-free survival (81.2% vs. 70.7%, p = 0.352) were comparable between the two groups. Moreover, results in the nCRT cohort were comparable to those in the overall cohort. CONCLUSIONS: Even with nCRT, TME combined with LPN dissection is safe and feasible for elderly patients, demonstrating low mortality and acceptable morbidity. Elderly and non-elderly patients with LPN metastasis who undergo LPN dissection can achieve comparable 3-year survival outcomes. TRAIL REGISTRATION: ClinicalTrials.gov Identifier: NCT04850027.

Single-cell and WGCNA uncover a prognostic model and potential oncogenes in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Single-cell transcriptome sequencing (scRNA-seq) can provide accurate gene expression data for individual cells. In this study, a new prognostic model was constructed by scRNA-seq and bulk transcriptome sequencing (bulk RNA-seq) data of CRC samples to develop a new understanding of CRC. METHODS: CRC scRNA-seq data were downloaded from the GSE161277 database, and CRC bulk RNA-seq data were downloaded from the TCGA and GSE17537 databases. The cells were clustered by the FindNeighbors and FindClusters functions in scRNA-seq data. CIBERSORTx was applied to detect the abundance of cell clusters in the bulk RNA-seq expression matrix. WGCNA was performed with the expression profiles to construct the gene coexpression networks of TCGA-CRC. Next, we used a tenfold cross test to construct the model and a nomogram to assess the independence of the model for clinical application. Finally, we examined the expression of the unreported model genes by qPCR and immunohistochemistry. A clone formation assay and orthotopic colorectal tumour model were applied to detect the regulatory roles of unreported model genes. RESULTS: A total of 43,851 cells were included after quality control, and 20 cell clusters were classified by the FindCluster () function. We found that the abundances of C1, C2, C4, C5, C15, C16 and C19 were high and the abundances of C7, C10, C11, C13, C14 and C17 were low in CRC tumour tissues. Meanwhile, the results of survival analysis showed that high abundances of C4, C11 and C13 and low abundances of C5 and C14 were associated with better survival. The WGCNA results showed that the red module was most related to the tumour and the C14 cluster, which contains 615 genes. Lasso Cox regression analysis revealed 8 genes (PBXIP1, MPMZ, SCARA3, INA, ILK, MPP2, L1CAM and FLNA), which were chosen to construct a risk model. In the model, the risk score features had the greatest impact on survival prediction, indicating that the 8-gene risk model can better predict prognosis. qPCR and immunohistochemistry analysis showed that the expression levels of MPZ, SCARA3, MPP2 and PBXIP1 were high in CRC tissues. The functional experiment results indicated that MPZ, SCARA3, MPP2 and PBXIP1 could promote the colony formation ability of CRC cells in vitro and tumorigenicity in vivo. CONCLUSIONS: We constructed a risk model to predict the prognosis of CRC patients based on scRNA-seq and bulk RNA-seq data, which could be used for clinical application. We also identified 4 previously unreported model genes (MPZ, SCARA3, MPP2 and PBXIP1) as novel oncogenes in CRC. These results suggest that this model could potentially be used to evaluate the prognostic risk and provide potential therapeutic targets for CRC patients.

Genetically predicted testosterone and cancers risk in men: a two-sample Mendelian randomization study.

OBJECTIVE: In observational studies, testosterone has been reported to be associated with some types of cancers. However, the direction and magnitude of the causal association between testosterone and different types of cancer remain unclear. This Mendelian randomization study assessed the causal associations of total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in men. METHODS: We performed two-sample Mendelian randomization using publicly available GWAS summary statistics to investigate the genetically causal association between testosterone and the risk of 22 kinds of cancers in men. Causal estimates were calculated by the inverse variance weighted method. We also performed additional sensitivity tests to evaluate the validity of the casualty. RESULTS: Genetically predicted BT level were significantly associated with an increased risk of prostate cancer [odds ratio (OR) = 1.17 95% confidence interval (CI): 1.09-1.26, P = 2.51E-05] in the MR analysis with the IVW method. TT was found to be the suggestive protective factor against stomach cancer (OR = 0.66, 95% CI: 0.48-0.93, P = 0.0116) as well as pancreatic cancer (OR = 0.59, 95% CI: 0.36-0.96, P = 0.0346). A suggestive association was found between TT and the occurrence of small intestine cancer (OR = 1.0004, 95% CI: 1.0001-1.0007, P = 0.0116). However, testosterone had no significant association with other cancers. CONCLUSION: This study investigated the role of testosterone in the development of prostate cancer, stomach cancer, pancreatic cancer, and small intestine cancer but found no strong association with the other cancers in men.

Prognostic significance of lateral pelvic lymph node dissection for middle-low rectal cancer patients with lateral pelvic lymph node metastasis: a propensity score matching study.

BACKGROUND: There is still controversy regarding the clinical value and significance of lateral pelvic lymph node (LPN) dissection (LPND). The present study aimed to investigate whether the addition of LPND to total mesorectal excision (TME) confers survival benefits in rectal cancer patients with clinical lateral pelvic node metastasis (LPNM). METHODS: From January 2015 to January 2021, a total of 141 rectal cancer patients with clinical evidence of LPNM who underwent TME + LPND were retrospectively analysed and divided into the LPNM group (n = 29) and the non-LPNM group (n = 112). The LPNM group was further subdivided into a high-risk LPNM group (n = 14) and a low-risk LPNM group (n = 15). Propensity score matching (PSM) was performed to minimize selection bias. The primary outcomes of this study were 3-year overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 141 patients undergoing LPND, the local recurrence rate of patients with LPNM was significantly higher than that of patients without LPNM both before (27.6% vs. 4.5%, P = 0.001) and after (27.6% vs. 3.4%, P = 0.025) PSM. Multivariate analysis revealed that LPNM was an independent risk factor for not only OS (HR: 3.06; 95% CI, 1.15-8.17; P = 0.025) but also DFS (HR: 2.39; 95% CI, 1.18-4.87; P = 0.016) in patients with LPNM after TME + LPND. When the LPNM group was further subdivided, multivariate logistic regression analysis showed that OS and DFS were significantly better in the low-risk group (obturator/internal iliac artery region and < 2 positive LPNs). CONCLUSION: Even after LPND, LPNM patients have a poor prognosis. Moreover, LPNM is an independent poor prognostic factor affecting OS and DFS after TME + LPND. However, LPND appears to confer survival benefits to specific patients with single LPN involvement in the obturator region or internal iliac vessel region. Furthermore, LPND may have no indication in stage IV patients and should be selected carefully.

The genomic and transcriptome characteristics of lung adenocarcinoma patients with previous breast cancer.

BACKGROUND: Breast cancer and lung cancer are the top two malignancies in the female population and the number of patients with breast cancer and subsequent primary lung cancer has increased significantly in recent years. However, the unique molecular characteristics of this group of patients remains unclear. PURPOSE: To identify the genomic and transcriptome characteristics of primary lung adenocarcinoma patients with previous breast cancer by comparison with single primary lung adenocarcinoma (SPLA) patients. METHODS: The tumor and normal pulmonary tissue specimens of ten primary pulmonary adenocarcinoma patients with previous breast cancer (multiple primary cancer, MPC) and ten SPLA patients were prospectively collected. The whole exome sequencing (WES) and RNA sequencing (RNA-seq) were performed to analyze the gene mutation and expression differences between MPC and SPC patients. RESULTS: The results of WES indicated that the mutations of TRIM73, DLX6 and CNGB1 only existed in MPC patients. The results of RNA-seq manifested the occurrence of second primary lung adenocarcinoma in breast cancer patients was closely associated with cytokine-cytokine receptor action, autophagy, PI3L-Akt, cAMP and calcium ion signaling pathways. Besides, the expression levels of FGF10 and VEGFA genes were significantly increased in MPC patients. CONCLUSION: The occurrence of second primary lung adenocarcinoma may be related to the cytokine-cytokine receptor action, autophagy, PI3L-Akt, cAMP and calcium ion signaling pathways. Furthermore, the mutations of TRIM73, DLX6 and CNGB1 and high expression of FGF10 and VEGFA might play an important role in the development of lung adenocarcinoma in breast cancer patients. However, more in-depth investigations are needed to verify above findings.

Risk factors and prognostic significance of postoperative complications following lateral pelvic lymph node dissection for rectal cancer: results of the multicenter lateral node study in China.

OBJECTIVE: Total mesorectal excision (TME) plus lateral pelvic lymph node (LPN) dissection (LPND) is a technically complex and challenging procedure with higher morbidity than TME alone. We aimed to investigate the risk factors for postoperative complications after TME + LPND, and the impact of complications on patient prognosis. METHODS: A total of 387 rectal cancer patients with clinical LPN metastasis (LPNM) who underwent TME + LPND at three institutions affiliated with the Chinese Lateral Node Collaborative Group were included. Logistic regression models were used to identify the risk factors for post-surgical complications, and the log-rank test was used to compare the prognosis. Severe complications were described as grade III-V. RESULTS: The incidence rates of overall complications and severe complications after TME + LPND were 15.2% (59/387) and 7.8% (30/387), respectively. Multivariate analysis showed that a duration of operation ≥260 min was an independent risk factor for both overall (odds ratio [OR] = 3.03, 95% confidence interval [CI] = 1.57-5.85, P = 0.001) and severe postoperative complications (OR = 2.67, 95% CI = 1.06-6.73, P = 0.037). The development of overall postoperative complications (P = 0.114) and severe postoperative complications (P = 0.298) had no significant impact on the overall survival. However, patients with overall complications (P = 0.015) or severe complications (P = 0.031) with a postoperative hospital stay >30 days had significantly an overall worse survival. CONCLUSION: A surgical duration of ≥260 min is a significant risk factor for both overall and severe postoperative complications after TME + LPND for middle-low rectal cancer. Furthermore, the development of overall complications or severe complications that require a postoperative hospital stay >30 days significantly worsens the prognosis.

Short- and long-term outcomes of laparoscopic versus open selective lateral pelvic lymph node dissection for locally advanced middle-low rectal cancer: Results of a multicentre lateral node study in China.

AIM: Lateral pelvic lymph node dissection (LPND) is a technically challenging procedure, and the safety and feasibility of laparoscopic LPND remains undetermined. Here, we compared the short- and long-term survival outcomes of laparoscopic LPND with those of open LPND. METHODS: From January 2012 to December 2019, locally advanced middle-low rectal cancer patients with clinical evidence of lateral pelvic lymph node metastasis (LPNM) who underwent total mesorectal excision with LPND at three institutions were included. Propensity score matching was used to minimize selection bias. The short-term and oncological outcomes of open and laparoscopic LPND were compared. RESULTS: Overall, 384 patients were enrolled into the study including 277 and 107 patients who underwent laparoscopic and open LPND, respectively. After matching, patients were stratified into laparoscopic (n = 100) and open (n = 100) LPND groups. Patients in the laparoscopic LPND group had a shorter operation time (255 vs. 300 min, p = 0.001), less intraoperative blood loss (50 vs. 300 ml, p < 0.001), lower incidence of postoperative complications (32.0% vs. 15.0%, p = 0.005), shorter postoperative hospital stay (8 vs. 14 days, p < 0.001), and excision of more lateral pelvic lymph nodes (9 vs. 7, p = 0.025) than those in the open LPND group. The 3-year overall survival (p = 0.581) and 3-year disease-free survival (p = 0.745) rates were similar between the groups, and LPNM was an independent predictor of survival. CONCLUSION: Laparoscopic LPND is technically safe and feasible with favourable short-term results and similar oncological outcomes as open surgery in selected patients.

Mesorectal excision with lateral lymph node dissection for mid-low rectal cancer with lateral lymph node metastasis: efficacy and prognostic analysis.

BACKGROUND: The aim of this study was to evaluate the efficacy of lateral pelvic lymph node (LPN) dissection (LPND) for rectal cancer patients with LPN metastasis (LPNM) and investigate the impact of LPNM on prognosis. METHODS: One hundred twenty-five matched pairs were selected and divided into the total mesorectal excision (TME) group and TME + LPND group for evaluation after propensity matching. RESULTS: No significant difference was observed in the 3-year local recurrence rate between the TME group and the TME + LPND group (10.7% vs 8.8%, P = 0.817); however, the rate of distant metastasis after TME + LPND was significantly higher (15.2% vs 7.2%, P = 0.044). When the mesorectal LN and LPN groups were subdivided, 3-year RFS was not significantly different between the internal LPN and N2 groups (57.1% vs. 55.3%, P = 0.613). There was no significant difference in RFS between the external group and the stage IV group (49.1% vs. 22.5%, P = 0.302), but RFS in the former group was significantly worse than that in the N2 group (49.1% vs. 55.3%, P = 0.044). CONCLUSION: Although patients with suspected LPNM can achieve satisfactory local control after TME + LPND, systemic metastases are more likely to develop after surgery. Patients limited to internal iliac and obturator LN metastasis appear to achieve a survival benefit from LPND and can be regarded as regional LN metastasis. However, patients with LPNM in the external and common iliac LN metastasis have a poor prognosis that is significantly worse than that of N2 and slightly better than that of stage IV, and LPND should be carefully selected.

High-grade postoperative complications affect survival outcomes of patients with colorectal Cancer peritoneal metastases treated with Cytoreductive surgery and Hyperthermic Intraperitoneal chemotherapy.

BACKGROUND: This study aimed to evaluate the impact of postoperative complications on long-term survival in patients with peritoneal metastasis (PM) arising from colorectal cancer (CRC) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Patients with PM arising from CRC treated with CRS and HIPEC were systematically reviewed at the China National Cancer Center and Huanxing Cancer Hospital from June 2017 to June 2019. High-grade complications that occurred within 30 days were defined as grade 3 to 4 events according to the Common Terminology Criteria for Adverse Events (CTCAE) classification. Univariate and multivariable Cox regression models for overall survival were created. Predictors of high-grade postoperative complications were evaluated with univariate and multivariate logistic regression analyses. RESULTS: In all, 86 consecutive cases were included in this study. Forty-one patients (47.7%) developed postoperative complications, while 22 patients (25.6%) experienced high-grade complications. No mortality occurred during the postoperative period. The median survival of all patients was 25 months, and the estimated 3-year overall survival (OS) rate was 35.0%. In the multivariable Cox regression analysis, a high peritoneal carcinomatosis index (PCI) score (HR, 1.07, 95% CI, 1.01-1.14; P=0.015) and grade 3-4 postoperative complications (HR, 1.86, 95% CI, 1.22-3.51; P=0.044) correlated with worse overall survival. High estimated blood loss (OR, 1.01, 95% CI, 1.01-1.02; P< 0.001) was identified as an independent risk factor for developing high-grade complications. CONCLUSION: Careful patient selection, high levels of technical skill and improved perioperative management are crucial to ensure patient survival benefits after CRS+HIPEC.

Neoadjuvant chemoradiotherapy followed by lateral pelvic lymph node dissection for rectal cancer patients: A retrospective study of its safety and indications.

BACKGROUND AND OBJECTIVES: There is no consensus on the safety and indications of lateral pelvic lymph node dissection (LPND) for patients with clinical lateral pelvic node metastasis (LPNM) after neoadjuvant chemoradiotherapy (nCRT). METHODS: We retrospectively analyzed 151 patients who underwent total mesorectal excision (TME) + LPND and divided them into two groups: nCRT group (n = 73) and non-nCRT group (n = 78). RESULTS: Thirty-one (20.5%) patients had LPNM by pathology. The operative time was significantly longer in the nCRT group (291.9 vs. 237.0 min, p < 0.001); however, the two groups had comparable intraoperative blood loss (87.3 vs. 78.9 ml, p = 0.607) and morbidity (19.2% vs. 15.7%, p = 0.537). Additionally, in the nCRT group, multivariate logistic regression analysis showed that poor/mucinous/signet adenocarcinoma (odds ratio [OR] = 6.65, 95% confidence interval [CI] = 1.03-43.03, p = 0.047) and post-nCRT LPN size ≥7 mm (OR = 26.67, 95% CI = 2.87-247.91, p = 0.004) were independent risk factors for pathological LPNM. CONCLUSION: nCRT before TME + LPND is safe and feasible with a comparably low mortality and acceptable morbidity. Poor/mucinous/signet adenocarcinoma and post-nCRT LPN size ≥7 mm were independent predictive factors of pathological LPNM after nCRT for rectal cancer patients with clinical LPNM, and patients with these characteristics should consider LPND after nCRT.

Neoadjuvant chemotherapy followed by hyperthermic intraperitoneal chemotherapy for patients with colorectal peritoneal metastasis: a retrospective study of its safety and efficacy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are effective routine treatments for colorectal peritoneal metastasis (PM). However, the safety and efficacy of neoadjuvant chemotherapy (NAC) before CRS+HIPEC are poorly understood. Therefore, this study aimed to assess the perioperative safety and long-term efficacy of NAC prior to CRS+HIPEC for patients with synchronous colorectal PM. METHODS: Patients with synchronous colorectal PM who received NAC prior to CRS+HIPEC were systematically reviewed at the China National Cancer Center and Huanxing Cancer Hospital from June 2017 to June 2019. The clinicopathologic characteristics, perioperative parameters, and survival rates of patients who underwent CRS+HIPEC with NAC (NAC group) and patients who underwent CRS+HIPEC without NAC (non-NAC group) were compared. RESULTS: The study enrolled 52 patients, with 20 patients in the NAC group and 32 in the non-NAC group. In the NAC group, the proportion of patients with a peritoneal carcinomatosis index (PCI) score < 12 was significantly higher than that in the non-NAC group (80.0% vs 50.0%, P = 0.031), and more patients achieved complete cytoreduction (80.0% vs 46.9%, P = 0.018). The two groups had comparable grade III/IV complications and similar reoperation and mortality rates (P > 0.05). However, patients who received NAC had lower platelet counts (151.9 vs 197.7 × 109/L, P = 0.036) and neutrophil counts (4.7 vs 7.2 × 109/L, P = 0.030) on postoperative day 1. More patients survived for 2 years in the NAC group than in the non-NAC group (67.4% vs 32.2%, respectively, P = 0.044). However, the completeness of cytoreduction score (HR, 2.99; 95% CI, 1.14-7.84; P = 0.026), rather than NAC, was independently associated with overall survival (OS) in the multivariate analysis after controlling for confounding factors. CONCLUSION: NAC administration before CRS+HIPEC can be regarded as safe and feasible for patients with colorectal PM with comparably low mortality rates and acceptable morbidity rates. Nevertheless, large-sample randomized controlled studies are needed to confirm whether the administration of NAC before CRS+HIPEC confers a survival benefit to patients.

Does the primary tumour location affect the prognosis of patients with colorectal cancer peritoneal metastases treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy?

BACKGROUND: The impact of primary tumour location on the prognosis of patients with peritoneal metastasis (PM) arising from colorectal cancer (CRC) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is rarely discussed, and the evidence is still limited. METHODS: Patients with PM arising from CRC treated with CRS and HIPEC at the China National Cancer Center and Huanxing Cancer Hospital between June 2017 and June 2019 were systematically reviewed. Clinical characteristics, pathological features, perioperative parameters, and prognostic data were collected and analysed. RESULTS: A total of 70 patients were divided into two groups according to either colonic or rectal origin (18 patients in the rectum group and 52 patients in the colon group). Patients with PM of a colonic origin were more likely to develop grade 3-4 postoperative complications after CRS+HIPEC (38.9% vs 19.2%, P = 0.094), but this difference was not statistically significant. Patients with colon cancer had a longer median overall survival (OS) than patients with rectal cancer (27.0 vs 15.0 months, P = 0.011). In the multivariate analysis, the independent prognostic factors of reduced OS were a rectal origin (HR 2.15, 95% CI 1.15-4.93, P = 0.035) and incomplete cytoreduction (HR 1.99, 95% CI 1.06-4.17, P = 0.047). CONCLUSION: CRS is a complex and potentially life-threatening procedure, and we suggest that the indications for CRS+HIPEC in patients with PM of rectal origin be more restrictive and that clinicians approach these cases with caution.