Pathological-Features-Modified TNM Staging System Improves Prognostic Accuracy for Rectal Cancer.

BACKGROUND: Variations in survival outcomes are observed in the eighth edition of the American Joint Committee on Cancer TNM staging system. OBJECTIVE: Machine learning ensemble methods were used to develop and evaluate the effectiveness of a pathological-features-modified TNM staging system in predicting survival for patients with rectal cancer by use of commonly reported pathological features, such as histological grade, tumor deposits, and perineural invasion, to improve the prognostic accuracy. DESIGN: This was a retrospective population-based study. SETTINGS: Data were assessed from the database of the Surveillance, Epidemiology, and End Results Program. PATIENTS: The study cohort comprised 14,468 patients with rectal cancer diagnosed between 2010 and 2015. The development cohort included those who underwent surgery as the primary treatment, whereas patients who received neoadjuvant therapy were assigned to the validation cohort. MAIN OUTCOME MEASURES: The primary outcome measures included cumulative rectal cancer survival, adjusted HRs, and both calibration and discrimination statistics to evaluate model performance and internal validation. RESULTS: Multivariable Cox regression analysis identified all 3 pathological features as prognostic factors, after which patients were categorized into 4 pathological groups based on the number of pathological features (ie, 0, 1, 2, and 3). Distinct survival differences were observed among the groups, especially with patients with stage III rectal cancer. The proposed pathological-features-modified TNM staging outperformed the TNM staging in both the development and validation cohorts. LIMITATIONS: Retrospective in design and lack of external validation. CONCLUSIONS: The proposed pathological-features-modified TNM staging could complement the current TNM staging by improving the accuracy of survival estimation of patients with rectal cancer. See Video Abstract . EL SISTEMA DE ESTADIFICACIN TNM CON CARACTERSTICAS PATOLGICAS MODIFICADO MEJORA LA PRECISIN DEL PRONSTICO DEL CNCER DE RECTO: ANTECEDENTES:Se observan variaciones en los resultados de supervivencia en el sistema de estadificación TNM del Comité Conjunto Americano del Cáncer 8º ediciónOBJETIVO:Se utilizaron métodos conjuntos de aprendizaje automático para desarrollar y evaluar la eficacia de un sistema de estadificación con características patológicas modificadas de tumores, ganglios y metástasis para predecir la supervivencia de pacientes con cáncer de recto, utilizando algunas características patológicas comúnmente informadas, como el grado histológico, depósitos tumorales e invasión perineural, para mejorar la precisión del pronóstico.DISEÑO:Este fue un estudio retrospectivo de base poblacional.ENTERNO CLINICO:Se recuperaron y evaluaron datos de la base de datos de Vigilancia, Epidemiología y Resultados Finales.PACIENTES:La cohorte del estudio estuvo compuesta por 14,468 pacientes con cáncer de recto diagnosticados entre 2010 y 2015. La cohorte de desarrollo incluyó a aquellos que se sometieron a cirugía como tratamiento primario, mientras que los pacientes que recibieron terapia neoadyuvante fueron asignados a la cohorte de validación.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas de resultado primarias incluyeron supervivencia acumulada del cáncer de recto, índices de riesgo ajustados y estadísticas de calibración y discriminación para evaluar el rendimiento del modelo y la validación interna.RESULTADOS:El análisis de regresión multivariable de Cox identificó las tres características patológicas como factores pronósticos, después de lo cual los pacientes se clasificaron en cuatro grupos patológicos según el número de características patológicas (es decir, 0, 1, 2 y 3). Se observaron distintas diferencias en la supervivencia entre los grupos, especialmente en los pacientes en estadio III. La estadificación propuesta con características patológicas modificadas de tumores-ganglios-metástasis superó a la estadificación TNM tanto en las cohortes de desarrollo como en las de validación.LIMITACIONES:Diseño retrospectivo y falta de validación externa.CONCLUSIONES:La estadificación propuesta con características patológicas modificadas de tumores-ganglios-metástasis podría complementar la estadificación TNM actual al mejorar la precisión de la estimación de supervivencia de los pacientes con cáncer de recto. (Traducción- Dr. Francisco M. Abarca-Rendon ).

Which treatment strategy is optimal for acute left-sided malignant colonic obstruction? A Bayesian meta-analysis.

PURPOSE: This study aimed to determine the best treatment for acute left-sided malignant colonic obstruction (ALMCO) among emergency surgery (ES), self-expanding metallic stent (SEMS), transanal drainage tube (TD), and decompressive stoma (DS). METHOD: Articles that compared two or more treatments of ALMCO were searched from PubMed, Cochrane Library, and Embase. Network meta-analyses were performed to calculate the outcomes of primary anastomosis, stoma creation, morbidity, mortality, and 5-year survival. RESULTS: Fifty-one articles met inclusion criteria. TD was the optimal treatment in performing primary anastomosis [probability of ranking first (Pro-1) 0.96], while ES was the worst [probability of ranking fourth (Pro-4) 0.99]. More permanent stoma was formed in ES and TD groups than in SEMS and DS groups [OR (95%CI): TD vs SEMS: 4.12 (1.89, 9.45); TD vs DS: 3.39 (1.46, 8.75); ES vs DS: 2.55 (1.73, 4.17); SEMS vs ES: 0.33 (0.24, 0.42)]. More morbidity occurred in ES group than in SEMS group [OR (95%CI): ES vs SEMS: 1.44 (1.14, 1.82)]. Besides, SEMS was ranked first in avoiding infection (Pro-4 0.95). For in-hospital mortality, ES was ranked first (Pro-1 0.93). TD was ranked first in recurrence (Pro-1 0.97) and metastasis (Pro-1 0.98). There was no discrepancy in 5-year overall and disease-free survival among all strategies. CONCLUSION: SEMS as a bridge to surgery reduces stoma formation, and morbidity especially the infection rate with relatively great oncological outcomes. Therefore, SEMS should be recommended first for ALMCO in the medical center with experience and conditions.

NF-κB downstream miR-1262 disturbs colon cancer cell malignant behaviors by targeting FGFR1.

Despite substantial advancements in screening, surgery, and chemotherapy, colorectal cancer remains the second most lethal form of the disease. Nuclear factor kappa B (NF-κB) signaling is a critical driver facilitating the malignant transformation of chronic inflammatory bowel diseases. In this study, deregulated miRNAs that could play a role in colon cancer are analyzed and investigated for specific functions in vitro using cancer cells and in vivo using a subcutaneous xenograft model. miRNA downstream targets are analyzed, and predicted binding and regulation are verified. miR-1262, an antitumor miRNA, is downregulated in colon cancer tissue samples and cell lines. miR-1262 overexpression suppresses colon cancer malignant behaviors in vitro and tumor development and metastasis in a subcutaneous xenograft model and a lung metastasis mouse model in vivo. miR-1262 directly targets fibroblast growth factor receptor 1 (FGFR1) and inhibits FGFR1 expression. FGFR1 overexpression shows oncogenic functions through the regulation of cancer cell proliferation, invasion, and migration; when cotransfected, lv-FGFR1 partially attenuates the antitumor effects of agomir-1262. NF-κB binds to the miR-1262 promoter region and inhibits transcription activity. The NF-κB inhibitor CAPE exerts antitumor effects; miR-1262 inhibition partially reverses CAPE effects on colon cancer cells. Conclusively, miR-1262 serves as an antitumor miRNA in colon cancer by targeting FGFR1. The NF-κB/miR-1262/FGFR1 axis modulates colon cancer cell phenotypes, including proliferation, invasion, and migration.

Tumor Deposits and Perineural Invasion had Comparable Impacts on the Survival of Patients With Non-metastatic Colorectal Adenocarcinoma: A Population-Based Propensity Score Matching and Competing Risk Analysis.

BACKGROUND: Both tumor deposits (TD) and perineural invasion (PNI) have been identified as risk factors for poor survival in patients with non-metastatic colorectal adenocarcinoma (CRC). However, the adverse impacts of TD and PNI on the survival of patients with non-metastatic CRC have not been compared. METHOD: Patients with non-metastatic CRC with known TD and PNI status were selected from the Surveillance, Epidemiology, and End Results (SEER) database. First, bivariate logistic regression analysis was utilized to identify the factors associated with TD and PNI status. Then, patients were divided into four groups, according to TD and PNI status. Propensity score matching (PSM) was performed to balance the baseline covariates. The impact of TD and PNI on survival was assessed by analyzing overall survival (OS) and cancer-specific mortality (CSM) rates. OS was calculated by the Kaplan-Meier method with log-rank analysis. CSM was estimated by competing risk analysis using the Fine and Gray model. RESULTS: A total of 70 689 patients with CRC met the inclusion and exclusion criteria. The positive rates of TD and PNI were 9.37% and 9.91%, respectively. For TD, the most important risk factor was N stage. With respect to PNI, the most significant factor was T stage. Tumor location, tumor size, differentiation grade, and serum CEA level were also correlated with TD and PNI status. After PSM, 1849 pairs were selected. Patients with TD+PNI+ status had the worst 5 year CSM and 5 year OS. In addition, the long-term survival outcomes of patients with TD+PNI- and TD-PNI+ status were comparable. CONCLUSION: The adverse impacts of TD and PNI on the survival of patients with non-metastatic CRC were comparable. CRC patients with both TD and PNI positive had the worst survival outcome.

The ratio of serum C-reactive protein level on postoperative day 3 to day 2 is a good marker to predict postoperative complications after laparoscopic radical gastrectomy for gastric cancer.

PURPOSE: Study reported that C-reactive protein (CRP) would peak at 48 h after the initiation of an acute inflammatory response. We proposed that the ratio of CRP level on postoperative day 3 to day 2 (POD3/2 CRP) can be used to early predict major postoperative complications (PCs) for patients who underwent laparoscopic radical gastrectomy. METHODS: Patients were randomized into training cohort and validation cohort at a ratio of 7:3. PCs greater than grade II or more, according to Clavien-Dindo classification, were defined as major PCs. Three predictive models for major PCs based on CRP level were constructed, including POD3/2 CRP, the CRP level on POD3 (POD3 CRP), and the ratio of CRP level on POD3 to POD1 (POD3/1 CRP). The performances of three prediction models were assessed by AUC. Univariate and multivariate logistic regression analyses were performed to identify risk factors of major PCs. RESULTS: 344 patients were included. Major PCs were observed in 57 patients (16.6%). In the training cohort, POD3/2 CRP provided the best diagnostic accuracy with an AUC of 0.929 at an optimal cut-off value of 1.08, and the sensitivity and specificity were 0.902 and 0.880, respectively. In the validation cohort, the corresponding AUC was 0.917. BMI ≥ 25 kg/m2 and POD3/2 CRP > 1 were identified as risk factors for major PCs. CONCLUSION: POD3/2 CRP is a reliable marker to predict major PCs after laparoscopic radical gastrectomy. If CRP is higher on POD3 than on POD2, major PCs are highly likely.

cMET promotes metastasis and epithelial-mesenchymal transition in colorectal carcinoma by repressing RKIP.

Increasing evidence indicates that c-mesenchymal-epithelial transition factor (cMET) plays an important role in the malignant progression of colorectal cancer (CRC). However, the underlying mechanism is not fully understood. As a metastasis suppressor, raf kinase inhibitory protein (RKIP) loss has been reported in many cancer types. In this study, the expression levels of cMET and RKIP in CRC tissues and cell lines were determined, and their crosstalk and potential biological effects were explored in vitro and in vivo. Our results showed that cMET was inversely correlated with RKIP. Both cMET upregulation and RKIP downregulation indicated poor clinical outcomes. Moreover, the MAPK/ERK signaling pathway was implicated in the regulation of cMET and RKIP. Overexpression of cMET promoted tumor cell epithelial-mesenchymal transition, invasion, migration, and chemoresistance, whereas the effects could be efficiently inhibited by increased RKIP. Notably, small hairpin RNA-mediated cMET knockdown dramatically suppressed cell proliferation, although no RKIP-induced influence on cell growth was observed in CRC. Altogether, cMET overexpression may contribute to tumor progression by inhibiting the antioncogene RKIP, providing preclinical justification for targeting RKIP to treat cMET-induced metastasis of CRC.

Long-term oncological outcomes of low anterior resection for rectal cancer with and without preservation of the left colic artery: a retrospective cohort study.

BACKGROUND: There is uncertainty in the literature about preserving the left colic artery (LCA) during low anterior resection for rectal cancer. We analyzed the effect of preserving the LCA on long-term oncological outcomes. METHODS: We retrospectively collected clinicopathological and follow-up details of patients who underwent low anterior resection for rectal cancer in the General Surgery Department of Guangdong Provincial People's Hospital, from January 2014 to December 2015. Cases were divided into low ligation (LL), LCA preserved, or high ligation (HL), LCA not preserved, of the inferior mesenteric artery. The 5-year overall survival (OS) and disease-free survival (DFS) rates were compared between the two groups. RESULTS: Altogether, there were 221 and 295 cases in the LL group and HL groups, respectively. Operating time in the LL group was significantly longer than in the HL group (224.7 vs. 211.7 min, p = 0.039). Postoperative 30-day mortality, early complications including anastomotic leakage showed no significant differences between the LL and HL groups (postoperative 30-day mortality, 0.9% LL, 1.4% HL, p = 0.884; early complications, 41.2% LL, 38.3% HL, p = 0.509; anastomotic leakage 8.6% LL, 13.2% HL, p = 0.100). The median follow-up periods were 51.4 (7-61) months in the LL group and 51.2 (8-61) months in the HL group. During follow-up, the percentages of patients who died, had local recurrence, or had metastases were 39.8, 7.7, and 38.5%, respectively, in the LL group and 39, 8.5, and 40%, respectively, in the HL group; these differences were not significant (all p > 0.05). The 5-year OS and DFS were 69.6 and 59.6% in the LL group, respectively, and 69.1 and 56.2% in the HL group, respectively; these differences were not significant (all p > 0.05). After stratification by tumor-node-metastasis stage, the difference between the 5-year OS and DFS for stages I, II, and III cancer were not significant (all p > 0.05). CONCLUSIONS: The long-term oncological outcomes of LL group are comparable with HL group. LL cannot be supported due to the absence of lower complication rates and the longer operating times.

Colon perforation due to cytomegalovirus infection in a patient with idiopathic hypereosinophilic syndrome: a case report.

BACKGROUND: Hypereosinophilic syndrome (HES) is a very rare disease and usually treated with corticosteroids. Gastrointestinal (GI) cytomegalovirus (CMV) infection is also rare but frequent in patients with immunocompromised status. These two related diseases present with similar manifestations, and may result in a life-threatening complication: perforation. However, the treatment strategies differ greatly. Here, we report a case of colon perforation due to cytomegalovirus infection in a patient with idiopathic HES. CASE PRESENTATION: A 41-year-old man with a history of HES was transferred to our hospital due to an acute onset of abdominal pain. During the treatment course of HES, this patient received CMV-DNA test with a result of < 2000 copies/ml. Computed tomography (CT) suggested colon perforation. An emergency surgery was performed immediately. Pathological diagnosis revealed CMV infection and infiltration of eosinophils. This patient received both anti-CMV therapy and immunosuppression therapy. Subsequently, the patient recovered and was discharged 25 days after the operation. CONCLUSION: During the course of HES treatment, CMV infection should be reconsidered if digestive symptoms relapse.

Is Preoperative Fibrinogen Associated with the Survival Prognosis of Gastric Cancer Patients? A Multi-centered, Propensity Score-Matched Retrospective Study.

BACKGROUND: The prognostic significance of preoperative plasma fibrinogen in patients with operable gastric cancer remains under debate. This study aimed to elucidate the prognostic value of fibrinogen in gastric cancer patients underwent gastrectomy. METHODS: A total of 4351 patients with gastric cancer collected from three comprehensive medical centers were retrospectively evaluated. Patients were categorized by minimum P value using X-tile, while the baseline confounders for fibrinogen was balanced through propensity score matching (PSM). The relationships between fibrinogen and other clinicopathologic features were evaluated, and nomogram was constructed to assess its prognostic improvement compared with TNM staging system. RESULTS: Fibrinogen was significantly correlated with macroscopic type, tumor differentiation, tumor size, and T and N stage. The factors, fibrinogen and T stage as well as N stage, were identified to be independent prognostic factors after PSM. Nomogram based on fibrinogen demonstrated a smaller Akaike information criterion (AIC) and a larger concordance index (C-index) than TNM staging system, illustrating that fibrinogen might be able to improve the prognostic accuracy. CONCLUSIONS: Preoperative plasma fibrinogen levels in gastric cancer patients were significantly correlated with tumor progression, which could be regarded as a reliable marker for survival prognostic prediction.

Oncometabolic surgery: Emergence and legitimacy for investigation.

Studies on morbid obesity have shown remarkable improvement of diabetes in patients who have undergone bariatric operations. It was subsequently shown that these operations induce diabetes remission independent of the resultant weight loss; as a result, surgeons began to investigate whether operations for gastric cancer (GC) could have the same beneficial effect on diabetes as bariatric operations. It was then shown in multiple reports that followed that certain operations for GC were able to improve or even cure type 2 diabetes mellitus (T2DM) in GC patients. This finding gave rise to the concept of "oncometabolic surgery", in which a patient diagnosed with both GC and T2DM undergo a single operation with the purpose of treating both diseases. With the increasing incidence of T2DM, oncometabolic surgery has the potential to improve the quality of life and even extend survival of many GC patients. However, because the GC patient population and the bariatric patient population are wildly different and because different GC operations have different properties, the effect of oncometabolic surgery must be carefully assessed and engineered in order to maximize benefit and avoid harm. This manuscript aims to summarize the findings made so far in the field of oncometabolic surgery and to provide an outlook regarding the possibility of oncometabolic surgery being incorporated into standard clinical practice.

Cinobufagin suppresses colorectal cancer angiogenesis by disrupting the endothelial mammalian target of rapamycin/hypoxia-inducible factor 1α axis.

Inducing angiogenesis is a hallmark of cancers that sustains tumor growth and metastasis. Neovascularization is a surprisingly early event during the multistage progression of cancer. Cinobufagin, an important bufadienolide originating from Chan Su, has been clinically used to treat cancer in China since the Tang dynasty. Here, we show that cinobufagin suppresses colorectal cancer (CRC) growth in vivo by downregulating angiogenesis. The hierarchized neovasculature is significantly decreased and the vascular network formation is disrupted in HUVEC by cinobufagin in a dose-dependent way. Endothelial apoptosis is observed by inducing reactive oxygen species (ROS) accumulation and mitochondrial dysfunction which can be neutralized by N-acetyl-l-cysteine (NAC). Expression of hypoxia-inducible factor 1α (HIF-1α) is reduced and phosphorylation of mTOR at Ser2481 and Akt at Ser473 is downregulated in HUVEC. Endothelial apoptosis is triggered by cinobufagin by stimulation of Bax and cascade activation of caspase 9 and caspase 3. Increased endothelial apoptosis rate and alterations in the HIF-1α/mTOR pathway are recapitulated in tumor-bearing mice in vivo. Further, the anti-angiogenesis function of cinobufagin is consolidated based on its pro-apoptotic effects on an EOMA-derived hemangioendothelioma model. In conclusion, cinobufagin suppresses tumor neovascularization by disrupting the endothelial mTOR/HIF-1α pathway to trigger ROS-mediated vascular endothelial cell apoptosis. Cinobufagin is a promising natural anti-angiogenetic drug that has clinical translation potential and practical application value.

Totally Laparoscopic Transluminal Resection for Gastrointestinal Stromal Tumors Located at the Cardiac Region.

BACKGROUND: The most common laparoscopic surgery for gastric gastrointestinal stromal tumors (GISTs) currently includes laparoscopic wedge resection, laparoscopic transgastric surgery, and laparoscopic intragastic surgery [Ohashi in Surg Endosc 9:169-171, 1995]. METHODS: The clinical data of 10 cases of cardiac endophytic GIST patients who received total laparoscopic intragastric surgery from June 2014 to March 2016 in Guangdong General Hospital were retrospectively analyzed. RESULTS: All cases were operated successfully without conversion to laparotomy. Operative time ranged from 59 to 104 min and blood loss was 5-65 mL. All specimens had intact capsules, diameters ranged from 16 to 26 mm, circumferential resection margins were 9-15 mm, and basement resection margins were 4-8 mm. All cases were pathologically diagnosed with GISTs. Time of flatus ranged from 1 to 4 days, time to resume eating was 2-4 days, drainage removal time was 3-4 days, and discharge time was 4-6 days. There was no postoperative hemorrhage, anastomotic leakage, cardiac stenosis, or other complications. All patients showed no swallowing disorders or acid reflux, and there were no signs of recurrence or metastasis in the follow-up period. CONCLUSION: Total laparoscopic intragastric treatment for cardiac endophytic GISTs is safe and feasible; however, an advanced laparoscopic surgical technique is required, which needs to be performed with caution.

Superiority of Tumor Location-Modified Lauren Classification System for Gastric Cancer: A Multi-Institutional Validation Analysis.

BACKGROUND: The tumor location-modified Lauren classification (mLC) has been proposed recently, but its clinical significance remains under debate. This study aimed to elucidate the clinical relevance of mLC and evaluate its superiority to the Lauren classification (LC) for gastric cancer patients with gastrectomy. METHODS: This study retrospectively evaluated 2764 consecutive gastric cancer patients from three comprehensive medical institutions. The patients were categorized into training, inner-validation, and independent validation sets. The relationships between mLC and other clinicopathologic factors were analyzed, and independent prognostic factors were identified. Survival prognostic discriminatory ability and predictive accuracy were compared between mLC and LC using the concordance index (C-index) and Akaike's information criterion (AIC), and a nomogram based on mLC was constructed to compare its prognostic improvement with the tumor-node metastasis (TNM) staging system. RESULTS: A significant association between mLC and gender, age, histologic type, T stage, N stage, and M stage was found. The findings showed that mLC, not LC, is an independent prognostic factor, with a smaller AIC and a higher C-index than LC. The nomogram based on mLC showed a better predictive ability than TNM alone. CONCLUSIONS: Compared with LC, mLC, which could be considered a more reliable prognostic factor, may improve the prognostic discriminatory ability and predictive accuracy for gastric cancer patients with gastrectomy.

Nomogram individually predicts the overall survival of patients with gastroenteropancreatic neuroendocrine neoplasms.

BACKGROUND: The current study aimed to establish a novel nomogram to predict the overall survival of individual Chinese patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Furthermore, this study sought to externally validate this nomogram using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: The records of 1183 patients with GEP-NENs treated at five high-capacity institutions in China between 2005 and 2015 were retrospectively analysed. In addition, 10 236 GEP-NEN cases from the SEER database were included as an external validation set. RESULTS: A multivariate analysis using Cox proportional hazards (PHs) regression was performed, and a nomogram was constructed. Discrimination, calibration, and external validation were performed using the SEER data set. The multivariate Cox model indicated that age, tumour size, differentiation, lymph node metastases, and distant metastases were independent covariates associated with survival. With respect to the training set, the nomogram exhibited better discrimination power than TNM classification (Harrell's concordance index (C-index): 0.837 vs 0.784, P=0.006). Discrimination was also excellent and superior to that of TNM classification for the SEER-based validation set (C-index: 0.808 vs 0.717, P<0.001). The calibrated nomogram predicted a survival rate that closely corresponded to the actual survival rate. CONCLUSIONS: We developed a nomogram that predicted the 3- and 5-year overall survival rates of patients with GEP-NENs. Validation revealed excellent discrimination and calibration for this nomogram, suggesting that it exhibits satisfactory clinical utility that might improve individualised predictions of survival risks and lead to the creation of additional clinical therapies.

Diagnosis and Treatment of 26 Cases of Abdominal Cocoon.

BACKGROUND AND AIMS: Abdominal cocoon (AC) is a rare abdominal disease with nonspecific clinical features, and it is difficult to be diagnosed before operation and hard to be treated in clinical practice. The aim of this study is to investigate the diagnosis and treatment of AC. METHODS: The clinical manifestations, findings during surgery, treatments, and follow-up results of 26 cases of AC were retrospectively studied from January 2001 to January 2015. RESULTS: All of 26 cases were diagnosed as AC definitely by laparotomy or laparoscopic surgery. Their clinical findings were various, with 7 intestines obstructed with bezoars and 4 intestines perforated by spiny material. Based on the existence of the second enterocoelia, all cases were categorized into 2 types: type I is absent of second enterocoelia (18 cases, 69.23%), while type II shows second enterocoelia (8 cases, 30.77%). Twenty cases (12 were type I and 8 were type II) underwent membrane excision and careful enterodialysis to release the small intestine entirely or partially, while the other 6 cases (all were type I) did not. In addition, all patients were treated with medical treatment and healthy diet and lifestyle. Finally, most of the patients recovered smoothly. CONCLUSIONS: AC can be categorized into two types; surgery is recommended for type II and part of type I with severe complications, but sometimes conservative therapy might be appropriate for type I. Laparoscopic surgery plays an important role in the diagnosis and treatment of AC. Furthermore, favorite health education, healthy diet and lifestyle are of significance in patients' recovery.

Laparoscopic hepatectomy for colorectal liver metastases located in all segments of the liver.

PURPOSE: Laparoscopic hepatectomy is not a well-established treatment modality for colorectal liver metastases. Moreover, most reports have been limited to tumors in the anterolateral segments (segments 2, 3, 4b, 5, and 6). In this study we evaluated the short- and long-term outcomes after laparoscopic hepatectomy for colorectal liver metastases located in all segments, including tumors located in the posterosuperior segments (segments 1, 4a, 7, and 8). METHODS: This retrospective study included 102 patients who underwent laparoscopic hepatectomy for colorectal liver metastases with radical intent between January 2009 and January 2016. The patients were divided into two groups (anterolateral and posterosuperior group) according to tumor location. The clinical and follow-up data of the two groups were reviewed. RESULTS: There was no 30-day postoperative mortality. Most of the postoperative 30-day complications were classified as minor complications (Clavien-Dindo classification). There was no difference in clinicopathologic characteristics between the two groups. Although posterosuperior group patients had significantly longer operative time (p=0.008) and postoperative hospital stay duration (p=0.041), as well as a greater blood loss (p=0.012), there was no significant difference in the rate and severity of postoperative complications (p=0.314 and 1.000 respectively). During a median follow-up of 41 months, the 5-year overall survival (OS) (p=0.449), and disease-free survival (DFS) (p=0.370) showed no significant difference between the two groups. CONCLUSIONS: Laparoscopic hepatectomy for colorectal liver metastases located in all segments of the liver can be safely performed in selected patients, with acceptable postoperative morbidity and oncologic results.

Laparoscopic hepatectomy for colorectal liver metastases located in all segments of the liver.

PURPOSE: Laparoscopic hepatectomy is not a well-established treatment modality for colorectal liver metastases. Moreover, most reports have been limited to tumors in the anterolateral segments (segments 2, 3, 4b, 5, and 6). We evaluated the short- and long-term outcomes after laparoscopic hepatectomy for colorectal liver metastases located in all segments, including tumors located in the posterosuperior segments (segments 1, 4a, 7, and 8). METHODS: TThis retrospective study included 102 patients who underwent laparoscopic hepatectomy for colorectal liver metastases with radical intent between January 2009 and January 2016. The patients were divided into two groups (anterolateral and posterosuperior group) according to tumor location. The clinical and follow-up data of the two groups were retrospectively reviewed. RESULTS: There was no 30-day postoperative mortality. Most of the postoperative 30-day complications were classified as minor complications (Clavien-Dindo classification). There was no difference in clinicopathologic characteristics between the two groups. Although posterosuperior group patients had significantly longer operative time (p=0.008) and postoperative hospital stay duration (p=0.041), as well as a greater blood loss (p=0.012), there was no significant difference in rate and severity of postoperative complications (p=0.314 and 1.000 respectively). During a median follow-up period of 41 months, the 5-year overall survival (OS) (p=0.449), and disease-free survival (DFS) (p=0.370) was no significant difference between the two groups. CONCLUSIONS: Laparoscopic hepatectomy for colorectal liver metastases located in all segments of the liver can be safely performed in selected patients, with acceptable postoperative morbidity and oncologic results.

Pax6 mediates ß-catenin signaling for self-renewal and neurogenesis by neocortical radial glial stem cells.

The Wnt/ß-catenin pathway is a critical stem cell regulator and plays important roles in neuroepithelial cells during early gestation. However, the role of Wnt/ß-catenin signaling in radial glia, a major neural stem cell population expanded by midgestation, remains poorly understood. This study shows that genetic ablation of ß-catenin with hGFAP-Cre mice inhibits neocortical formation by disrupting radial glial development. Reduced radial glia and intermediate progenitors are found in the ß-catenin-deficient neocortex during late gestation. Increased apoptosis and divergent localization of radial glia in the subventricular zone are also observed in the mutant neocortex. In vivo and in vitro proliferation and neurogenesis as well as oligodendrogenesis by cortical radial glia or by dissociated neural stem cells are significantly defective in the mutants. Neocortical layer patterning is not apparently altered, while astrogliogenesis is ectopically increased in the mutants. At the molecular level, the expression of the transcription factor Pax6 is dramatically diminished in the cortical radial glia and the sphere-forming neural stem cells of ß-catenin-deficient mutants. Chromatin immunoprecipitation and luciferase assays demonstrate that ß-catenin/Tcf complex binds to Pax6 promoter and induces its transcriptional activities. The forced expression of Pax6 through lentiviral transduction partially rescues the defective proliferation and neurogenesis by ß-catenin-deficient neural stem cells. Thus, Pax6 is a novel downstream target of the Wnt/ß-catenin pathway, and ß-catenin/Pax6 signaling plays critical roles in self-renewal and neurogenesis of radial glia/neural stem cells during neocortical development.

CPE correlates with poor prognosis in gastric cancer by promoting tumourigenesis.

Aims: To investigate the potential functions and mechanisms of tumourigenesis in carboxypeptidase E (CPE) and its prognostic value in gastric cancer, and to develop a predictive model for prognosis based on CPE. Results: Transcriptome level variation and the prognostic value of CPE in different types of cancers were investigated using bioinformatics analyses. The association between CPE and clinicopathological characteristics was specifically explored in gastric cancer. Elevated CPE expression was associated with poor survival and recurrence prognosis and was found in cases with a later clinical stage of gastric cancer. The CPE was considered an independent prognostic factor, as assessed using Cox regression analysis. The prognostic value of CPE was further verified through immunohistochemistry and haematoxylin staining. Enrichment analysis provided a preliminary confirmation of the potential functions and mechanisms of CPE. Immune cell infiltration analysis revealed a significant correlation between CPE and macrophage infiltration. Eventually, a prognosis prediction nomogram model based on CPE was developed. Conclusion: CPE was identified as an independent biomarker associated with poor prognosis in gastric cancer. This suggests that CPE overexpression promoted epithelial-mesenchymal transition via the activation of the Erk/Wnt pathways, leading to proliferation, invasion, and metastasis. Targeted therapeutic strategies for gastric cancer may benefit from these findings.

Prognostic impact of tumor budding in rectal cancer after neoadjuvant therapy: a systematic review and meta-analysis.

BACKGROUND: Tumor budding (TB) is a negative prognostic factor in colorectal cancer; however, its prognostic impact following neoadjuvant therapy for patients with rectal cancer remains unclear. This study aims to assess the prognostic impact of TB and the correlation between TB and other pathological features in patients with rectal cancer after neoadjuvant therapy. METHODS: A comprehensive search of PubMed, Embase, Cochrane, Scopus, CNKI, Wanfang, and ClinicalKey databases was conducted for studies on the prognosis of TB in rectal cancer after neoadjuvant therapy from the inception of the databases to January 2023, and the final literature included was determined using predefined criteria. Quality assessment of the studies included, extraction of general and prognostic information from them, and meta-analyses were carried out progressively. RESULTS: A total of 11 studies were included, and the results of the meta-analysis showed that high-grade tumor budding (TB-1) increased the risk of poor 5-year disease-free survival (HR = 1.75, 95% CI 1.38-2.22, P < 0.00001), 5-year overall survival (HR = 1.77, 95% CI 1.21-2.59, P = 0.003), local recurrence (OR = 4.15, 95% CI 1.47-11.75, P = 0.007), and distant metastasis (OR = 5.36, 95% CI 2.51-11.44, P < 0.0001) in patients with rectal cancer after neoadjuvant therapy. TB-1 was significantly associated with poor differentiation and lymphatic, perineural, and venous invasion. CONCLUSION: Tumor budding is significantly correlated with unfavorable prognosis and poor pathological characteristics following neoadjuvant therapy for rectal cancer. We anticipate more high-quality, prospective studies in the future to confirm our findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022377564.