Construction and validation of machine learning models for predicting distant metastases in newly diagnosed colorectal cancer patients: A large-scale and real-world cohort study.

BACKGROUND: More accurate prediction of distant metastases (DM) in patients with colorectal cancer (CRC) would optimize individualized treatment and follow-up strategies. Multiple prediction models based on machine learning have been developed to assess the likelihood of developing DM. METHODS: Clinicopathological features of patients with CRC were obtained from the National Cancer Center (NCC, China) and the Surveillance, Epidemiology, and End Results (SEER) database. The algorithms used to create the prediction models included random forest (RF), logistic regression, extreme gradient boosting, deep neural networks, and the K-Nearest Neighbor machine. The prediction models' performances were evaluated using receiver operating characteristic (ROC) curves. RESULTS: In total, 200,958 patients, 3241 from NCC and 197,717 CRC from SEER were identified, of whom 21,736 (10.8%) developed DM. The machine-learning-based prediction models for DM were constructed with 12 features remaining after iterative filtering. The RF model performed the best, with areas under the ROC curve of 0.843, 0.793, and 0.806, respectively, on the training, test, and external validation sets. For the risk stratification analysis, the patients were separated into high-, middle-, and low-risk groups according to their risk scores. Patients in the high-risk group had the highest incidence of DM and the worst prognosis. Surgery, chemotherapy, and radiotherapy could significantly improve the prognosis of the high-risk and middle-risk groups, whereas the low-risk group only benefited from surgery and chemotherapy. CONCLUSION: The RF-based model accurately predicted the likelihood of DM and identified patients with CRC in the high-risk group, providing guidance for personalized clinical decision-making.

Prognostic model for predicting the survival benefit of adjuvant chemotherapy for elderly patients with stage II colon cancer: a population-based study.

OBJECTIVES: Adjuvant chemotherapy benefits in elderly patients with stage II colon cancer (CC) remain controversial. We aimed to construct a nomogram to estimate the chemotherapy survival benefits in elderly patients. METHODS: The training and testing cohort were patients with stage II CC older than 70 years from the Surveillance, Epidemiology, and End Results (SEER) database, while the external validation cohort included patients from the National Cancer Center (NCC). Cox proportional hazard models were used to determine the covariates associated with overall survival (OS). Using the risk factors identified by Cox proportional hazards regression, a nomogram was developed to predict OS. Nomogram precision was assessed using receiver operating characteristic and calibration curves. RESULTS: The present study recruited 42 097 and 504 patients from the SEER database and NCC, respectively. The OS of patients who underwent surgery plus adjuvant chemotherapy was considerably longer than patients who underwent surgery alone. The nomogram included variables related to OS, including age, year of diagnosis, sex, AJCC T stage, tumor location, tumor size, harvested lymph nodes, and chemotherapy. According to the nomogram score, the elderly patients were separated into high- and low-risk groups, with high-risk group nomogram scores being greater than the median value, and vice versa. Patients in the high-risk group witnessed worse prognosis and were more likely to benefit from postoperative chemotherapy. CONCLUSION: This nomogram can be regarded as a useful clinical tool for assessing the potential adjuvant chemotherapy benefits and for predicting survival in elderly patients with stage II CC.

Enlarged tumour-draining lymph node with immune-activated profile predict favourable survival in non-metastatic colorectal cancer.

BACKGROUND: The tumour-draining lymph node (TDLN) plays a pivotal role in the suppression of malignant tumour, however, the immunological profile and prognostic differences between large TDLN (L-TDLN) and small TDLN (S-TDLN) in colorectal cancer (CRC) remain unclear. METHODS: We conducted a study using data from the Chinese National Cancer Center (CNCC) database, identifying 837 CRC patients with non-metastatic TDLN, and categorised them into L-TDLN and S-TDLN groups. The long-term survival outcomes and adjuvant therapy efficacy were compared between the two groups. Furthermore, we evaluated the differences in immune activation status and immune cell subsets between patients in L-TDLN and S-TDLN groups by RNA sequencing and immunohistochemical (IHC) staining. RESULTS: Patients with L-TDLN demonstrated better long-term outcomes compared to those with S-TDLN. Among patients with L-TDLN, there was no significant difference in long-term outcomes between those who received adjuvant chemotherapy and those who did not. The RNA sequencing data revealed a wealth of immune-activating pathways explored in L-TDLN. Furthermore, IHC analysis demonstrated higher numbers of CD3+ and CD8 + T cells in L-TDLN and the corresponding CRC lesions, as compared to patients with S-TDLN. CONCLUSION: Enlarged TDLN exhibited an activated anti-tumour immune profile and may serve as an indicator for favourable survival in non-metastatic CRC.

Comparison of short- and long-term outcomes between laparoscopic and open multivisceral resection for clinical T4b colorectal cancer: A multicentre retrospective cohort study in China.

BACKGROUND: Laparoscopic surgery is controversial for patients with clinical T4b colorectal cancer (CRC) who require multivisceral resection (MVR). This study aims to explore and compare the safety and long-term oncological outcomes of laparoscopic surgery and open surgery for patients with clinical T4b CRC. MATERIALS AND METHODS: This study was a retrospective cohort study based on a multicentre database. According to the operation method, the patients were divided into a laparoscopic MVR group and an open MVR group. The short-term and long-term outcomes were compared. RESULTS: From January 2010 to December 2021, a total of 289 patients in the laparoscopic MVR group and 349 patients in the open MVR group were included. After propensity score matching, patients were stratified into a laparoscopic MVR group (n = 163) and an open MVR group (n = 163). Compared with the open MVR group, the laparoscopic MVR group had less blood loss (100 vs. 200, p < 0.001), a shorter time to first flatus (3 vs. 4, P < 0.001), a shorter postoperative hospital stay (10 vs. 12, P < 0.001), and a lower incidence of surgical site infection (2.5 % vs. 8.0 %, P = 0.043). The Kaplan-Meier curves showed that the two groups had similar overall survival (P = 0.283) and disease-free survival (P = 0.152). CONCLUSION: Compared with open MVR, laparoscopic MVR had less blood loss, fewer surgical site infection complications, faster recovery and a shorter hospital stay. The long-term survival outcome of laparoscopic MVR was not inferior to that of open MVR.

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.

Short-Term and Long-Term Outcomes of Intracorporeal Anastomosis in Laparoscopic Segmental Left Colectomy for Splenic Flexure Cancer-a Multicenter Retrospective Cohort Study of 342 cases.

INTRODUCTION: While intracorporeal anastomosis (IA) has been widely used in totally laparoscopic right colectomy, its application in laparoscopic segmental left colectomy for splenic flexure cancer remains underexplored, particularly in large-scale studies with long-term outcomes. This research aims to assess the technical feasibility and oncological efficacy of IA in treating colonic splenic flexure carcinoma, drawing insights from both short-term and long-term outcomes of a retrospective cohort. MATERIALS AND METHODS: A retrospective analysis was conducted on 342 patients diagnosed with colonic splenic flexure carcinoma in three Chinese medical centers. These patients underwent laparoscopic segmental left colectomy between December 2014 and December 2019 across three medical institutions. Comprehensive data encompassing demographics, disease features, pathological characteristics, operative details, and both short and long-term outcomes were gathered and scrutinized. Using propensity scores, each patient from the IA cohort was paired with a counterpart from the extracorporeal anastomosis (EA) cohort. RESULTS: IA was performed on 129 patients, while 213 underwent EA. Post-propensity score matching resulted in 129 matched pairs. After matching, many baseline characteristics were balanced. The IA cohort exhibited several advantages including shorter incision lengths (P<0.001), more extensive proximal and distal resection margins (P=0.003, P<0.001). Additionally, the IA method facilitated a more rapid postoperative recovery as indicated by quicker return of bowel movements (resumption of passing flatus [2.7 (1.0-7.0) days vs. 3.3 (2.0-8.0) days, P<0.001] and defecation [3.7 (1.0-9.0)] days vs. 4.5 (2.0-9.0) days, P<0.001]), faster discharges [6.6 (3.0-15.0) days vs. 8.3 (5.0-20.0) days, P<0.001], and decreased need for rescue analgesics (P<0.001). The rate of postoperative complications, as rated by the Clavien-Dindo classification, remained consistent across both techniques (P=0.087). Furthermore, the cosmetic outcome rated by Patient Scar Assessment Questionnaire and Scoring System (PSAQ) was markedly superior in the IA group (P<0.001). Both approaches demonstrated equivalent 5-year overall (82.7% vs. 82.1%, P=0.419) and disease-free survival (80.9% vs. 78.1%, P=0.476). Subsequent stratification analysis revealed that IA achieved comparable 5-year overall (80.7% vs. 82.0%, P=0.647) and disease-free survival (78.1% vs. 76.4%, P=0.734) in patients with locally advanced colon cancer. CONCLUSION: Employing IA for laparoscopic segmental left colectomy in cases of splenic flexure carcinoma is not only safe but also offers enhanced cosmetic results and expedited postoperative recovery. Oncologically speaking, IA in left segmental colectomy for splenic flexure carcinoma can yield therapeutic outcomes comparable to those of EA, even in patients with locally advanced colon cancer.

Natural orifice specimen extraction surgery versus small-incision assisted laparoscopic radical right hemicolectomy.

Conventional laparoscopic-assisted right hemicolectomy requires a small abdominal incision to extract the specimen, which becomes an important source of postoperative complications and impairs perioperative experience. Transvaginal natural orifice specimen extraction surgery (NOSES VIIIA) avoids this small incision by extracting the specimen through the vagina. Here we describe the design of a multicenter, open-label, parallel, noninferior, phase III randomized controlled trial (NCT05495048). The aim of this study is to confirm that the NOSES VIIIA procedure is not inferior to small-incision assisted right hemicolectomy in long-term oncological efficacy. A total of 352 female patients with right colon adenocarcinoma/high-grade intraepithelial neoplasia will be randomly assigned to the NOSES VIIIA arm and the small-incision arm in a 1:1 ratio. The primary end point of this trial is 3 year disease-free survival. Clinical Trial Registration: NCT05495048 (ClinicalTrials.gov).

Predictive Value of the Neutrophil-Lymphocyte Ratio for Tumor Regression Grade and Prognosis of Local Advanced Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy.

PURPOSE: Numerous indicators can be used to predict tumor patients' prognosis and tumor regression grade (TRG). The role of the neutrophil-lymphocyte ratio (NLR) among individuals with locally advanced rectal cancer (LARC) following neoadjuvant chemoradiotherapy (nCRT) hasn't been studied, nevertheless. This study aims to explore the predictive value of the NLR before nCRT (pre-NLR) in TRG and prognosis of LARC patients undergoing nCRT.. METHODS: In this retrospective investigation, 326 LARC patients receiving nCRT in total were included. The link between the pre-NLR and TRG was examined using a logistic regression analysis. A Cox-based nomogram was created in the meanwhile to forecast overall survival (OS). With the use of calibration plots and receiver operating characteristic (ROC) curves, we evaluated the nomogram's predictive capabilities. RESULTS: The median pre-NLR across 326 patients was 2.2 (interquartile range, IQR: 1.7-2.7). In the logistic regression analysis, only the pre-NLR for TRG in LARC patients receiving nCRT was statistically significant (odds ratio, OR = 0.62, 95% CI: 0.47-0.80, P < 0.001). Pre-NLR, nCRT with surgery interval, ypTNM stage, TRG, vascular invasion, adjuvant chemotherapy, and carbohydrate antigen 19-9 before nCRT were revealed to be OS predictors in the Cox multivariate analysis. According to calibration plots and ROC curves, the predictive nomogram demonstrated high statistical performance on internal validation. CONCLUSION: This study demonstrated that a lower pre-NLR was probably associated with a greater rate of TRG in LARC patients undergoing nCRT. Furthermore, the pre-NLR was credibly correlated with OS in LARC patients undergoing nCRT. Meanwhile, we constructed a nomogram for predicting the prognosis in LARC patients undergoing nCRT.

Short- and long-term results of open vs laparoscopic multisegmental resection and anastomosis for synchronous colorectal cancer located in separate segments.

BACKGROUND: It remains unclear whether laparoscopic multisegmental resection and anastomosis (LMRA) is safe and advantageous over traditional open multisegmental resection and anastomosis (OMRA) for treating synchronous colorectal cancer (SCRC) located in separate segments. AIM: To compare the short-term efficacy and long-term prognosis of OMRA as well as LMRA for SCRC located in separate segments. METHODS: Patients with SCRC who underwent surgery between January 2010 and December 2021 at the Cancer Hospital, Chinese Academy of Medical Sciences and the Peking University First Hospital were retrospectively recruited. In accordance with the inclusion and exclusion criteria, 109 patients who received right hemicolectomy together with anterior resection of the rectum or right hemicolectomy and sigmoid colectomy were finally included in the study. Patients were divided into the LMRA and OMRA groups (n = 68 and 41, respectively) according to the surgical method used. The groups were compared regarding the surgical procedure's short-term efficacy and its effect on long-term patient survival. RESULTS: LMRA patients showed markedly less intraoperative blood loss than OMRA patients (100 vs 200 mL, P = 0.006). Compared to OMRA patients, LMRA patients exhibited markedly shorter postoperative first exhaust time (2 vs 3 d, P = 0.001), postoperative first fluid intake time (3 vs 4 d, P = 0.012), and postoperative hospital stay (9 vs 12 d, P = 0.002). The incidence of total postoperative complications (Clavien-Dindo grade: ≥ II) was 2.9% and 17.1% (P = 0.025) in the LMRA and OMRA groups, respectively, while the incidence of anastomotic leakage was 2.9% and 7.3% (P = 0.558) in the LMRA and OMRA groups, respectively. Furthermore, the LMRA group had a higher mean number of lymph nodes dissected than the OMRA group (45.2 vs 37.3, P = 0.020). The 5-year overall survival (OS) and disease-free survival (DFS) rates in OMRA patients were 82.9% and 78.3%, respectively, while these rates in LMRA patients were 78.2% and 72.8%, respectively. Multivariate prognostic analysis revealed that N stage [OS: HR hazard ratio (HR) = 10.161, P = 0.026; DFS: HR = 13.017, P = 0.013], but not the surgical method (LMRA/OMRA) (OS: HR = 0.834, P = 0.749; DFS: HR = 0.812, P = 0.712), was the independent influencing factor in the OS and DFS of patients with SCRC. CONCLUSION: LMRA is safe and feasible for patients with SCRC located in separate segments. Compared to OMRA, the LMRA approach has more advantages related to short-term efficacy.

Development and validation of an artificial intelligence prediction model and a survival risk stratification for lung metastasis in colorectal cancer from highly imbalanced data: A multicenter retrospective study.

BACKGROUND: To assist clinicians with diagnosis and optimal treatment decision-making, we attempted to develop and validate an artificial intelligence prediction model for lung metastasis (LM) in colorectal cancer (CRC) patients. METHODS: The clinicopathological characteristics of 46037 CRC patients from the Surveillance, Epidemiology, and End Results (SEER) database and 2779 CRC patients from a multi-center external validation set were collected retrospectively. After feature selection by univariate and multivariate analyses, six machine learning (ML) models, including logistic regression, K-nearest neighbor, support vector machine, decision tree, random forest, and balanced random forest (BRF), were developed and validated for the LM prediction. In addition, stratified LM patients by risk score were utilized for survival analysis. RESULTS: Extremely low rates of LM with 2.59% and 4.50% were present in the development and validation set. As the imbalanced learning strategy, the BRF model with an Area under the receiver operating characteristic curve (AUC) of 0.874 and an average precision (AP) of 0.184 performed best compares with other models and clinical predictor. Patients with LM in the high-risk group had significantly poorer survival (P＜0.001) and failed to benefit from resection (P = 0.125). CONCLUSIONS: In summary, we have utilized the BRF algorithm to develop an effective, non-invasive, and practical model for predicting LM in CRC patients based on highly imbalanced datasets. In addition, we have implemented a novel approach to stratify the survival risk of CRC patients with LM based the output of the model.

Identification of MKI67, TPR , and TCHH Mutations as Prognostic Biomarkers for Patients With Defective Mismatch Repair Colon Cancer Stage II/III.

BACKGROUND: Stage II/III disease is the most predominant form of colorectal cancer, accounting for approximately 70% of cases. Furthermore, approximately 15% to 20% of patients with stage II/III disease have deficient mismatch repair or microsatellite instability-high colorectal cancer. However, there are no identified significant prognostic biomarkers for this disease. OBJECTIVE: To identify prognostic markers for patients with deficient mismatch repair/microsatellite instability-high colon cancer stage II/III. DESIGN: Retrospective study design. SETTING: The study was conducted at a high-volume colorectal center, the Cancer Hospital, Chinese Academy of Medical Sciences. PATIENTS: Patients diagnosed with stage II/III deficient mismatch repair/microsatellite instability-high colon cancer who underwent curative surgery at the Cancer Hospital at the Chinese Academy of Medical Sciences between July 2015 and November 2018 were included. MAIN OUTCOME MEASURES: The primary outcome measure was the influence of differentially mutated genes on progression-free survival. RESULTS: The retrospective deficient mismatch repair/microsatellite instability-high cohort involved 32 patients and The Cancer Genome Atlas-microsatellite instability-high cohort involved 45 patients. Patients with deficient mismatch repair/microsatellite instability-high colon cancer had higher mutational frequencies of MKI67 , TPR , and TCHH than patients with microsatellite stable colon cancer. MKI67 , TPR , TCHH , and gene combination were significantly correlated with prognosis. The biomarker mutation-type colon cancer group had a higher risk of recurrence or death than did the wild-type group. Moreover, biomarker mutation-type tumors had more mutations in the DNA damage repair pathway and tumor mutational burden than did biomarker wild-type tumors. LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: MKI67 , TPR , and TCHH may serve as potential diagnostic and prognostic biomarkers for deficient mismatch repair/microsatellite instability-high colon cancer stage II/III. IDENTIFICACIN DE MUTACIONES MKI, TPR Y TCHH COMO BIOMARCADORES PRONSTICOS PARA PACIENTES CON CNCER DE COLON EN ETAPA II/III CON DEFICIENCIA EN LA REPARACION DE ERRORES DE EMPAREJAMIENTO: ANTECEDENTES:La enfermedad en estadio II/III es la forma más predominante de cáncer colorrectal y representa aproximadamente el 70% de los casos. Además, aproximadamente entre el 15% y el 20% de los pacientes con enfermedad en estadio II/III tienen reparación deficiente de errores de emparejamiento o inestabilidad de microsatélital alta. Sin embargo, no se han identificado biomarcadores pronósticos significativos para esta enfermedad.OBJETIVO:Este estudio tuvo como objetivo identificar marcadores pronósticos para pacientes con cáncer de colon con reparación deficiente de errores de emparejamiento/inestabilidad microsatelital alta en estadio II/III.DISEÑO:Diseño de estudio retrospectivo.ESCENARIO:El estudio se realizó en un centro colorrectal de alto volumen, el Hospital del Cáncer de la Academia China de Ciencias Médicas.PACIENTES:Pacientes diagnosticados con cáncer de colon en estadio II/III con reparación deficiente de errores de emparejamiento o inestabilidad de microsatélital alta que se sometieron a cirugía curativa en el Hospital del Cáncer de la Academia China de Ciencias Médicas entre julio de 2015 y noviembre de 2018.MEDIDAS DE RESULTADO PRINCIPALES:La medida de resultado primaria fue la influencia de los genes con mutaciones diferenciales en la supervivencia libre de progresión.RESULTADOS:La cohorte retrospectiva de reparación deficiente de errores de emparejamiento o inestabilidad de microsatélital alta y la cohorte de inestabilidad microsatelital alta del Atlas del Genoma del Cáncer involucraron a 32 y 45 pacientes, respectivamente. Los pacientes con de reparación deficiente de errores de emparejamiento/inestabilidad microsatélital alta tuvieron frecuencias mutacionales más altas de MKI67 , TPR y TCHH que los pacientes estables de microsatélites. MKI67 , TPR , TCHH , y la combinación de genes se correlacionaron significativamente con el pronóstico. El grupo de cáncer de colon de tipo mutación de biomarcador tenía un mayor riesgo de recurrencia o muerte que el grupo de mutación salvaje. Además, los tumores de tipo mutación de biomarcadores tenían más mutaciones en la vía de reparación del daño del ADN y la carga mutacional del tumor que los tumores de tipo salvaje de biomarcadores.LIMITACIONES:Este estudio estuvo limitado por su naturaleza retrospectiva.CONCLUSIONES:MKI67 , TPR , y TCHH pueden servir como posibles biomarcadores de diagnóstico y pronóstico para cáncer de colon en estadio II/III con reparación deficiente de errores de emparejamiento/inestabilidad microsatélital alta. (Traducción-Dr. Jorge Silva Velazco ).

Preliminary surgical outcomes of laparoscopic right hemicolectomy with transrectal specimen extraction: a propensity score matching study of 120 cases (with video).

Background: Compared with conventional laparoscopic surgery, natural orifice specimen extraction surgery (NOSES) has many advantages. Laparoscopic right colectomy with transvaginal specimen extraction has been reported, but the safety and feasibility of transrectal specimen extraction in male patients with ascending colon cancer remain to be verified. This study aimed to preliminarily evaluate the feasibility and safety of laparoscopic right hemicolectomy with transrectal specimen extraction. Methods: The study was conducted at a single tertiary medical center in China. A total of 494 consecutive patients who underwent laparoscopic right colectomy between September 2018 and September 2020 were included. Transrectal specimen extraction was performed in 40 male patients (the NOSES group). Patients in the NOSES group were matched to the conventional laparoscopic group using propensity score matching at a 1:2 ratio. Short-term and long-term outcomes between the two groups were compared and evaluated. Results: Forty patients in the NOSES group and 80 patients in the conventional laparoscopic group were matched for analysis. Baseline characteristics were balanced after propensity matching. The operative features, including operating time, intraoperative bleeding, and the number of harvested lymph nodes, were statistically comparable in both groups. In terms of post-operative recovery, patients in the NOSES group showed preferable outcomes, as evidenced by less post-operative pain and faster return to flatus, defecation, and discharge. The post-operative complications rate, according to the Clavien-Dindo classification system, was similar in both groups. No differences in overall survival or disease-free survival were observed between the two groups. Conclusions: Laparoscopic right colectomy with transrectal specimen extraction is oncologically safe. Compared with conventional laparoscopic right colectomy, it can reduce post-operative pain, accelerate post-operative recovery, shorten the hospital stay, and achieve better cosmetic effect.

Persistent descending mesocolon as a vital risk factor for anastomotic failure and prolonged operative time for sigmoid colon and rectal cancers.

BACKGROUND: The diagnostic criteria and effect of persistent descending mesocolon (PDM) on sigmoid and rectal cancers (SRCs) remain controversial. This study aims to clarify PDM patients' radiological features and short-term surgical results. METHOD: From January 2020 to December 2021, radiological imaging data from 845 consecutive patients were retrospectively analyzed using multiplanar reconstruction (MRP) and maximum intensity projection (MIP). PDM is defined as the condition wherein the right margin of the descending colon is located medially to the left renal hilum. Propensity score matching (PSM) was used to minimize database bias. The anatomical features and surgical results of PDM patients were compared with those of non-PDM patients. RESULTS: Thirty-two patients with PDM and 813 patients with non-PDM were enrolled into the study who underwent laparoscopic resection. After 1:4 matching, patients were stratified into PDM (n = 27) and non-PDM (n = 105) groups. The lengths from the inferior mesenteric artery (IMA) to the inferior mesenteric vein (1.6 cm vs. 2.5 cm, p = 0.001), IMA to marginal artery arch (2.7 cm vs. 8.4 cm, p = 0.001), and IMA to the colon (3.3 cm vs. 10.2 cm, p = 0.001) were significantly shorter in the PDM group than those in the non-PDM group. The conversion to open surgery (11.1% vs. 0.9%, p = 0.008), operative time (210 min vs. 163 min, p = 0.001), intraoperative blood loss (50 ml vs. 30 ml, p = 0.002), marginal arch injury (14.8% vs. 0.9%, p = 0.006), splenic flexure free (22.2% vs. 3.8%, p = 0.005), Hartmann procedure (18.5% vs. 0.0%, p < 0.001) and anastomosis failure (18.5% vs. 0.9%, p = 0.001) were significantly higher in the PDM group. Moreover, PDM was an independent risk factor for prolonged operative time (OR = 3.205, p = 0.004) and anastomotic failure (OR = 7.601, p = 0.003). CONCLUSION: PDM was an independent risk factor for prolonged operative time and anastomotic failure in SRCs surgery. Preoperative radiological evaluation using MRP and MIP can help surgeons better handle this rare congenital variant.

Genome-wide discovery of circulating cell-free DNA methylation biomarkers for colorectal cancer detection.

BACKGROUND: Colorectal polyp is known a precursor of colorectal cancer (CRC) that holds an increased risk for progression to CRC. Circulating cell-free DNA (cfDNA) methylation has shown favorable performance in the detection and monitoring the malignant progression in a variety of cancers. RESULTS: To discover cfDNA methylation markers for the diagnosis of CRC, we first performed a genome-wide analysis between eight CRC and eight polyp tissues using the Infinium HumanMethylationEPIC BeadChip. We identified 7008 DMCs, and after filtering, we validated 39 DMCs by MethylTarget sequencing in 62 CRC and 56 polyp tissues. A panel of four CpGs (cg04486886, cg06712559, cg13539460, and cg27541454) was selected as the methylation marker in tissue by LASSO and random forest models. A diagnosis prediction model was built based on the four CpGs, and the methylation diagnosis score (md-score) can effectively discriminate tissues with CRC from polyp patients (AUROC > 0.9). Finally, the cg27541454 was confirmed hypermethylated in CRC (AUC = 0.85) in the plasma validation cohort. CONCLUSIONS: Our findings suggest that the md-score could robustly detect CRC from polyp tissues, and cg27541454 may be a promising candidate noninvasive biomarker for CRC early diagnosis.

Optimal examined lymph node number for accurate staging and long-term survival in rectal cancer: a population-based study.

BACKGROUND: Although the recommended minimal examined lymph node (ELN) number in rectal cancer (RC) is 12, this standard remains controversial because of insufficient evidence. We aimed to refine this definition by quantifying the relationship between ELN number, stage migration and long-term survival in RC. METHODS: Data from a Chinese multi-institutional registry (2009-2018) and the Surveillance, Epidemiology, and End Results (SEER) database (2008-2017) on stages I-III resected RC were analysed to determine the relationship between ELN count, stage migration, and overall survival (OS) using multivariable models. The series of odds ratios (ORs) for negative-to-positive node stage migration and hazard ratios (HRs) for survival with more ELNs were fitted using a Locally Weighted Scatterplot Smoothing (LOWESS) smoother, and structural breakpoints were determined using the Chow test. The relationship between ELN and survival was evaluated on a continuous scale using restricted cubic splines (RCS). RESULTS: The distribution of ELN count between the Chinese registry ( n =7694) and SEER database ( n =21 332) was similar. With increasing ELN count, both cohorts exhibited significant proportional increases from node-negative to node-positive disease (SEER, OR, 1.012, P <0.001; Chinese registry, OR, 1.016, P =0.014) and serial improvements in OS (SEER: HR, 0.982; Chinese registry: HR, 0.975; both P <0.001) after controlling for confounders. Cut-point analysis showed an optimal threshold ELN count of 15, which was validated in the two cohorts, with the ability to properly discriminate probabilities of survival. CONCLUSIONS: A higher ELN count is associated with more precise nodal staging and better survival. Our results robustly conclude that 15 ELNs are the optimal cut-off point for evaluating the quality of lymph node examination and stratification of prognosis.

FGF19-Induced Inflammatory CAF Promoted Neutrophil Extracellular Trap Formation in the Liver Metastasis of Colorectal Cancer.

Liver metastasis is the main cause of death in patients with colorectal cancer (CRC); thus, necessitating effective biomarkers and therapeutic targets for colorectal cancer liver metastasis (CRLM). Fibroblast growth factor 19 (FGF19) is a protumorigenic gene in numerous human malignancies. In this study, it is shown that FGF19 plays an indispensable role in CRLM. FGF19 expression and secretion are markedly correlated with liver metastasis and lower overall survival rates of patients with CRC. An in vivo metastasis model shows that FGF19 overexpression confers stronger liver-metastatic potential in CRC cells. Mechanistically, FGF19 exerts an immunomodulatory function that creates an environment conducive for metastasis in CRLM. FGF19 mediates the polarization of hepatic stellate cells to inflammatory cancer-associated fibroblasts (iCAFs) by activating the autocrine effect of IL-1α via the FGFR4-JAK2-STAT3 pathway. FGF19-induced iCAFs promote neutrophil infiltration and mediate neutrophil extracellular trap (NET) formation in liver metastatic niches via the production of complement C5a and IL-1ß, which in turn accelerates the liver colonization of CRC cells. Importantly, targeting FGF19 signaling with fisogatinib efficiently suppresses FGF19-induced liver metastasis in a mouse model. In summary, this study describes the mechanism by which FGF19 regulates CRLM, thereby providing a novel target for CRLM intervention.

Laparoscopic radical transverse colectomy with transrectal specimen extraction: A novel natural orifice specimen extraction procedure: A case report.

Transverse colon cancer accounts for about 10% of all colonic cancers. The resection of cancers in the transverse colon is technically more challenging, compared with other cancer locations in the colon because the variable anatomy of the middle colic vessels demands excellent surgical skills and the anatomical location of the transverse colon is related to major organs. We report a novel laparoscopic technique for the first time used in surgery of transverse colon cancer which combines a total intracorporeal anastomosis with natural orifice specimen extraction to solve the problems of traditional laparoscopic surgery. A 48-year-old male patient, whose diagnosis was transverse colon adenocarcinoma, was admitted to the hospital. The surgery was performed in accordance with the procedure of totally laparoscopic right hemicolectomy and the specimen was extracted by opening the rectum. Natural orifice specimen extraction surgery has many advantages, including less pain, better cosmesis and minimising risks of complications and also has comparable long-term outcomes compared to conventional laparoscopic surgery.

Case Report: Transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy for gastric cancer in a patient with situs inversus totalis: with video.

Because of its significant advantage of fast postoperative recovery, natural orifice specimen extraction surgery (NOSES) has attracted increasing attention worldwide. However, the NOSES in gastric cancer (GC) treatment still needs more clinical practice, especially for the rare anatomical anomaly. Situs inversus totalis (SIT) is a rare autosomal recessive anatomical anomaly with an incidence ranging between 1/8,000 and 1/25,000 births. We present a video of transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy performed in a 59-year-old woman known to have SIT. Preoperative investigations revealed that the patient had early GC at the antrum. A gastroscopy report from the local hospital showed signet-ring cell carcinoma. The preoperative computed tomography scan revealed irregular thickening of the gastric wall at the junction of the greater curvature and antrum without metastasis to the lymph nodes. In total, laparoscopic D2 distal gastrectomy was performed with transvaginal specimen extraction. Billroth II with Braun anastomosis was performed for reconstruction. The length of the operation was 240 min without intraoperative complications and with minimal blood loss of 50 ml. The patient was uneventfully discharged on postoperative Day 7. The final pathology confirmed signet-ring cell carcinoma confined to the mucosal muscle without metastasis in 16 lymph nodes. Transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy can be safely performed in patients with SIT and has similar surgical outcomes to usual laparoscopic gastrectomy.

Comparative short-term and survival outcomes of three specimen extraction techniques in laparoscopic low rectal cancer surgery: does it affect ileostomy closure?

INTRODUCTION: This study aimed to compare the short-term and survival outcomes in laparoscopic low rectal cancer surgery with three different specimen extraction techniques, and whether it affects loop ileostomy closure. MATERIALS AND METHODS: A consecutive series of patients with low rectal cancer who underwent laparoscopic low anterior resection plus protective loop ileostomy (LAR-PLI) were enrolled. Three main techniques, namely specimen extraction through auxiliary incision (EXAI), specimen extraction through stoma incision (EXSI), and specimen eversion and extra-abdominal resection (EVER), were employed. The postoperative short-term and survival outcomes of the three techniques and the impact on loop ileostomy closure were compared. RESULTS: In all, 254 patients were enrolled in this study: 104 (40.9%) in the EXAI group, 104 (40.9%) in the EXSI group, and 46 (18.1%) in the EVER group. For primary surgery, EXAI group had significantly longer operative time (P < 0.001), more intraoperative bleeding (P < 0.001), longer length of abdominal incision (P<0.001), longer time to first flatus (P < 0.001), longer time to first defecation (P < 0.001), longer time to first eat (P < 0.001), and longer postoperative hospital stays (P = 0.005) than the EXSI and EVER groups. The primary postoperative complication rate in the EXAI and EVER group was significantly higher than in the EXSI group (P = 0.005). In loop ileostomy closure, EXAI group had significantly longer operative time (P = 0.001), more bleeding volume, and longer postoperative hospital stays (P < 0.001) than the EXSI and EVER groups. For survival outcomes, the 3-year local recurrence-free survival (LRFS) is 92.6% for all patients. The 3-year LRFS for patients in EXAI, EXSI, and EVER were 90.1%, 95.4%, and 92.7%, with P = 0.476. CONCLUSIONS: Our single-center results found that in LAR-PLI surgery for low rectal cancer, the short-term outcomes of specimen extraction through the stoma incision or anus were better than that through the auxiliary incision, but the 3-year LRFS was no statistically different.