Monocyte/macrophage mediates the impact of depression on Crohn's disease.

BACKGROUND: Depression increases the risk of Crohn's disease (CD) and worsens its prognosis. Monocytes/macrophages, immune modulate cells, play vital roles in both depression and CD. OBJECTIVES: We investigated whether monocyte/macrophage could mediate the impact of depression on CD through induction of CD4 + T lymphocyte differentiation and epithelial barrier dysfunction, in addition to the alteration of their own phagocytic ability and cytokines production. METHODS: Circulating monocytes and intestinal macrophages were isolated from eligible CD patients, divided into depressed and non-depressed groups. Phagocytosis was determined using flow cytometry while in vitro cytokine production was quantified using Luminex assay and qPCR. CD4 + T cells were cocultured with monocytes, then Type 1 Helper T Lymphocytes Th1/Type 2 Helper T Lymphocytes (Th2) /Type 17 Helper T Lymphocytes (Th17)/Treg subsets were analyzed using flow cytometry and qPCR. Caco-2 monolayers simulating epithelial barrier were cocultured with macrophages, and integrity and proliferation were evaluated. Tight junction protein expression was detected using immunofluorescence and western blot. RESULTS: Decreased monocyte/macrophage phagocytosis and enhanced production of pro-inflammatory cytokines including Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and Interleukin-1ß (IL-1ß) were revealed in the depressed versus non-depressed CD groups. Higher proportions of Th1 and Th17 cells with a lower proportion of Treg cell were observed after cocultured with monocytes from the depressed versus non-depressed CD patients. So were the expressions of their corresponding transcription factors T-bet, Retinoic Acid Related Orphan Nuclear Receptor gamma T (RORγt) and Forkhead box protein P3 (FoxP3). Caco-2 cells cocultured with macrophages from depressed CD displayed lower Transepithelial electric resistance (TEER), reduced proliferation activity, and decreased tight junction protein expressions compared with their counterpart cocultured with macrophages from non-depressed CD. CONCLUSIONS: Monocyte/macrophage may underlie the impact of depression upon CD via decreased phagocytosis, increased pro-inflammatory cytokine production, inducing CD4 + T cell differentiation toward Th1/Th17 cells rather than Treg cell, and impairing macrophage-enhanced epithelial barrier.

Predicting Rectal Cancer Response to Total Neoadjuvant Treatment Using an Artificial Intelligence Model Based on Magnetic Resonance Imaging and Clinical Data.

PURPOSE: To develop a model for predicting response to total neoadjuvant treatment (TNT) for patients with locally advanced rectal cancer (LARC) based on baseline magnetic resonance imaging (MRI) and clinical data using artificial intelligence methods. METHODS: Baseline MRI and clinical data were curated from patients with LARC and analyzed using logistic regression (LR) and deep learning (DL) methods to predict TNT response retrospectively. We defined two groups of response to TNT as pathological complete response (pCR) versus non-pCR (Group 1), and high sensitivity [tumor regression grade (TRG) 0 and TRG 1] versus moderate sensitivity (TRG 2 or patients with TRG 3 and a reduction in tumor volume of at least 20% compared to baseline) versus low sensitivity (TRG 3 and a reduction in tumor volume <20% compared to baseline) (Group 2). We extracted and selected clinical and radiomic features on baseline T2WI. Then we built LR models and DL models. Receiver operating characteristic (ROC) curves analysis was performed to assess predictive performance of models. RESULTS: Eighty-nine patients were assigned to the training cohort, and 29 patients were assigned to the testing cohort. The area under receiver operating characteristics curve (AUC) of LR models, which were predictive of high sensitivity and pCR, were 0.853 and 0.866, respectively. Whereas the AUCs of DL models were 0.829 and 0.838, respectively. After 10 rounds of cross validation, the accuracy of the models in Group 1 is higher than in Group 2. CONCLUSION: There was no significant difference between LR model and DL model. Artificial Intelligence-based radiomics biomarkers may have potential clinical implications for adaptive and personalized therapy.

Predictive value of apparent diffusion coefficient for neoadjuvant chemotherapy in locally advanced colorectal cancer patients.

Background: The efficacy of neoadjuvant chemotherapy is closely related to the long-term prognosis of colorectal cancer (CRC) patients. Apparent diffusion coefficient (ADC) is an index in dynamic enhanced magnetic resonance imaging (MRI), reflecting the density of tumor cells. ADC has been shown to be related to the efficacy of neoadjuvant chemotherapy in other malignant tumors, but there is still a lack of relevant research in CRC patients. Methods: A total of 128 patients with CRC treated with neoadjuvant chemotherapy in The First Affiliated Hospital of Xiamen University from January 2016 to January 2017 were retrospectively collected. According to the response after neoadjuvant chemotherapy, the patients were divided into an objective response group (n=80) and a control group (n=48). The clinical characteristics and ADC levels of the two groups were compared, and the predictive value of ADC on the efficacy of neoadjuvant chemotherapy was analyzed. The patients were followed up for 5 years to observe the difference of survival rate between the two groups, and further analyzed the correlation between ADC and survival rate. Results: Compared with the control group, the tumor size in the objective response group was significantly reduced (3.32±1.60 vs. 5.07±2.19 cm, P=0.000); ADC significantly increased (1.23±0.18 vs. 0.98±0.18 ×10-3 mm2/s, P=0.000); albumin significantly increased (39.32±4.14 vs. 37.46±4.18 g/L, P=0.016); the proportion of patients with poorly differentiated or undifferentiated tumor cells was significantly lower (51.25% vs. 72.92%, P=0.016); and the 5-year mortality decreased significantly (40.00% vs. 58.33%, P=0.044). ADC had the highest predictive value of objective response for locally advanced CRC patients after neoadjuvant chemotherapy, and the area under the curve (AUC) was 0.834 [95% confidence interval (CI): 0.765-0.903, P=0.000]; ADC had certain predictive value for the 5-year survival of locally advanced CRC patients, and the AUC was 0.778 (95% CI: 0.696-0.861, P=0.000). ADC >1.055×10-3 mm2/s, tumor size <4.1 cm, and moderately or well differentiated tumors were favorable factors for patients with locally advanced CRC to obtain objective response after neoadjuvant chemotherapy (P<0.05). Conclusions: ADC could be used as a predictor of the efficacy of neoadjuvant chemotherapy in locally advanced CRC patients.

Pathological response and safety of FOLFOXIRI for neoadjuvant treatment of high-risk relapsed locally advanced colon cancer: study protocol for a single-arm, open-label phase II trial.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) has been demonstrated effective in several tumours, but its benefit has not yet been elucidated in colorectal cancer, especially locally advanced colorectal cancer (LACRC). METHODS AND ANALYSIS: This is a single-arm, open-label, prospective phase II exploratory clinical trial. Patients with LACRC will receive four cycles of NAC with 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI), followed by operation and then adjuvant chemotherapy with capecitabine and oxaliplatin for two to five cycles or single-agent capecitabine for five cycles, or observation. The primary endpoint is the rate of tumour regression grade (TRG) 0-2 in the resected tumour tissue, which is evaluated by experienced pathologists according to the Ryan R TRG grading system. Secondary endpoints include objective response rate, pathologic complete response, microscopically complete resection rate, progression-free survival, distant metastasis-free survival, overall survival, toxicity and compliance to study treatment, molecular markers, quality of life to study treatment and the number of patients with 30-day postoperative mortality. The objective of this study is to analyse the efficacy and safety of FOLFOXIRI as the NAC regimen in patients with LACRC and to identify a promising treatment strategy in this setting. ETHICS AND DISSEMINATION: Written informed consent will be required from and provided by all patients enrolled. The study protocol has been approved by the independent ethics committee of West China Hospital, Sichuan University (approval number: 2021403). This study will demonstrate the potential benefit of NAC with the FOLFOXIRI regimen. Results will be shared with policymakers and the academic community to promote the clinical management of colon cancer. TRIAL REGISTRATION NUMBER: NCT05018182.

Sustained co-delivery of 5-fluorouracil and cis-platinum via biodegradable thermo-sensitive hydrogel for intraoperative synergistic combination chemotherapy of gastric cancer.

Gastric cancer is the fifth most common cancer and the third leading cause of cancer death worldwide, posing a severe threat to human health. Surgical resection remains the most preferred option for gastric cancer treatment. However, for advanced gastric cancer, the curative effect of surgical resection is usually limited by the local recurrence, peritoneal carcinomatosis, or distal metastasis. Intraoperative chemotherapy is an attractive in situ adjuvant treatment strategy to reduce the recurrence and metastasis after surgical resection. Here, we designed a 5-fluorouracil (5-FU) and cis-platinum (DDP) co-delivery system based on a biodegradable temperature-sensitive hydrogel (PDLLA-PEG-PDLLA, PLEL) for intraoperative adjuvant combination chemotherapy of gastric cancer. This 5-FU + DDP/PLEL hydrogel system characterized by a special sol-gel phase transition in response to physiological temperature and presented sustained drug release in vitro and in vivo. A strong synergistic cell proliferation inhibition and apoptosis promotion of 5-FU + DDP/PLEL were observed against gastric cancer MKN45-luc cells. After intraperitoneal injection, the dual-drug loaded hydrogel formulation showed superior anti-tumor effects than the single-drug carrying hydrogels and combination of free 5-FU and DDP on the gastric cancer peritoneal carcinomatosis model. The use of hydrogel for dual-drug delivery had benefited to fewer side effects as well. What's more, we established a mouse model for postsurgical residual tumors and peritoneal carcinomatosis of gastric cancer, in which the intraoperative administration of 5-FU + DDP/PLEL also remarkably inhibited the local recurrence of the orthotopic tumors and the growth of the abdominal metastatic tumors, resulting in an extended lifetime. Hence, this developed dual-drug loaded hydrogel system has great potential in the intraoperative chemotherapy of gastric cancer, that suggests a clinically-relevant and valuable option for postsurgical management of gastric cancer.

Effect of gasless endoscopic thyroidectomy through an axillary approach on the recurrent laryngeal nerve injury in patients with thyroid cancer.

OBJECTIVE: To observe the effect of gasless endoscopic thyroidectomy through an axillary approach (GETAN) on the recurrent laryngeal nerve in patients with thyroid cancer. METHODS: One hundred and ten patients with thyroid cancer admitted to the department of general surgery, the First Affiliated Hospital of Xiamen University were retrospectively selected as the research subjects. They were divided into an observation group (OG, 55 patients, treated with GETAN) and a control group (CG, 55 patients, treated with conventional radical resection for papillary thyroid cancer). Clinical indicators, pain degree, negative emotions, recurrent laryngeal nerve injury, vocal and swallowing function, and the incidence of complications were compared between the two groups. RESULTS: In terms of clinical indicators, the operation time, intraoperative blood loss, extubation time, and hospitalization time in the OG were shorter than those of the CG (all P<0.05). The scores of Visual Analogue Scale (VAS) at one, two, and three days after surgery in the OG were lower than those in the CG (all P<0.001). As for the negative emotions, the Self-Rating Anxiety Scale score, and Self-Rating Depression Scale score in the OG were lower than those in the CG (both P<0.001). The incidence of postoperative recurrent laryngeal nerve injury in the OG was lower than that of the CG (P<0.001). Another analysis showed that GETAN was a protective factor against recurrent laryngeal nerve injury in patients with thyroid cancer (P<0.05). The Voice Handicap Index and Swallowing impairment score one week and one month after surgery were lower in the OG than in the CG (all P<0.001). The incidence of postoperative complications such as hypocalcemia, wound infection, and numbness of hands and feet in the OG was lower than that in the CG (all P<0.001). CONCLUSION: The GETAN approach is able to relieve postoperative pain, anxiety, and depression; reduce the laryngeal recurrent nerve injury; promote the recovery of laryngeal recurrent nerve; and decrease the incidence of vocal and swallowing dysfunction It is worthy of clinical promotion.

Complete response to sotorasib as neoadjuvant treatment in patient with locally advanced primary pulmonary sarcoma harboring KRAS mutation: a case report.

Background: Primary pulmonary sarcoma (PPS) is very rare relative to other subtypes of lung cancer. Therefore, evidence-based treatment options for PPS patients have remained unclear. Identification of actionable cancer driver mutations in patients with non-small cell lung cancer (NSCLC) has provided the chance to use targeted treatments and improve patient clinical outcomes. In addition to epidermal growth factor receptor (EGFR), the wide use of high-throughput genomic profiling with next-generation sequencing (NGS) has also identified other cancer driver genes such as Kirsten rat sarcoma (KRAS), human epidermal growth factor receptor 2 (HER2), and mesenchymal epithelial transition (MET). Case Description: In our study, we reported a locally advanced PPS patient harboring KRAS G12C mutation. The clinical stage before neoadjuvant treatment was stage IIIB (c.T3N2M0). The direct KRAS G12C inhibitor sotorasib (AMG-510) was used as neoadjuvant treatment and the patient achieved complete response (CR). Then, the patient underwent video-assisted thoracoscopic surgery (VATS) with reserved spontaneous breathing for surgical resection. The pathological evaluation was indicative of pathological CR (pCR). Further follow-ups are required to evaluate the long-term clinical benefit of neoadjuvant treatment with sotorasib and surgical resection with VATS. Conclusions: To our knowledge, it was the first study to use sotorasib for a PPS patient harboring KRAS G12C mutation in a neoadjuvant setting. Further follow-ups are required to evaluate the long-term clinical benefit of neoadjuvant treatment with sotorasib and surgical resection with VATS.

Impact of Upfront Chemotherapy on the Effect of Primary Tumour Resection for Asymptomatic Synchronous Colorectal Cancer With Unresectable Metastases: A Propensity-Score-Matched Cohort Analysis.

Background: It is controversial whether primary tumour resection (PTR) and the sequencing of chemotherapy and PTR are associated with the survival of patients with incurable stage IV colorectal cancer. This study aimed to explore the effects of PTR and the sequencing of chemotherapy and PTR on asymptomatic colorectal cancer with synchronous unresectable metastases (asmCRC). Patients and Methods: Patients with asmCRC were retrospectively identified from a single centre and categorised into 3 groups: PTR followed by chemotherapy (POC), upfront chemotherapy followed by PTR (UFC), and palliative chemotherapy (PC). The primary end points included median overall survival (OS) and progression-free survival (PFS). Clinical features were analysed using χ2 test, while survival curves were generated using the Kaplan-Meier test. Propensity-score matching (PSM) was performed when comparing survival between POC and UFC groups. Results: From 2008 to 2014, 255 patients were identified and included into the POC (n = 101), UFC (n = 40), and PC (n = 114) groups. The UFC and POC groups had significantly better median OS compared with the PC group (40.7 vs 16.3 months, P < .0001; 39.7 vs 16.3 months, P < .0001). Before PSM, the UFC group had better median PFS than the POC and PC groups (18.5 vs 9.7 months, P = .038; 18.5 vs 6.1 months, P < .0001). After PSM, UFC has better PFS than POC (P = .038). And the UFC group did not have higher postoperative or preoperative morbidity compared with the POC group (P = .235). Conclusions: Primary tumour resection could improve the survival of patients with asmCRC. Compared with POC or PC, UFC was associated with a better median PFS without significantly increasing preoperative or postoperative morbidity.

Neoadjuvant treatment of sintilimab plus hypofractionated radiotherapy for MSI-H/dMMR rectal cancer: A prospective, multicenter, phase Ib study.

BACKGROUND: Neoadjuvant radiochemotherapy followed by radical surgery is the standard treatment strategy for local advanced rectal cancer (LARC). However, the efficacy of neoadjuvant radiochemotherapy is limited, especially for patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer. Considering the amazing therapeutic effect of immune check point inhibitors for metastatic colorectal cancer, we conduct this multicenter, phase Ib study to investigate the safety and efficacy of anti-PD-1 antibody, sintilimab combined with hypofractionated radiotherapy in MSI-H/dMMR rectal cancer patients. METHODS: Patients with MSI-H/dMMR LARC will receive hypofractionated radiotherapy (5 Gy × 5) and three cycles of sintilimab 200 mg IV every 2 weeks. Radical surgery will be performed 6-8 weeks after radiotherapy. The primary endpoint is adverse reaction after neoadjuvant treatment and perioperative complications. Secondary endpoints include pathological response rate, complete resection rate, and quality of life. DISCUSSION: This is the first study to investigate the safety and effectiveness of neoadjuvant radiotherapy combined with immunotherapy for MSI-H/dMMR LARC. It is expected that this study will propose a brand new and effective treatment strategy for MSI-H/dMMR LARC.

Early response to upfront neoadjuvant chemotherapy (CAPOX) alone in low- and intermediate-risk rectal cancer: a single-arm phase II trial.

BACKGROUND: With local recurrence of rectal cancer continuing to decrease, distant recurrence is becoming a major concern, especially for patients with low- and intermediate-risk stage II/III rectal cancer. Therefore, a new treatment strategy is warranted for these patients. This single-arm phase II trial aimed to assess the effect of neoadjuvant chemotherapy (NCT) in low- and intermediate-risk stage II/III rectal cancer and explore candidate radiological and clinical parameters for early prediction of tumour response after two cycles of CAPOX. METHODS: Patients with mid-low stage II/III rectal cancer with low and intermediate risk were examined. The primary outcome was defined as a clinicopathological response by integrating tumour longitudinal length reduction (TLLR) on MRI into pathological tumour regression grade (TRG). After completing NCT, patients with TRG0-2 and TRG3 with a TLLR rate greater than 30 per cent were considered to be responders. Secondary outcomes included pathological complete response (pCR), adverse events and local and distant recurrence. RESULTS: This study enrolled 61 eligible patients. No patient was converted to neoadjuvant chemoradiotherapy owing to tumour progression. The clinicopathological response and pCR rates were 78.7 and 21.3 per cent respectively. After two cycles of CAPOX, TLLR, TRG on MRI, and mucosal lesion regression grade on endoscopy had potential discriminative ability (area under the curve greater than 0.7) for predicting both clinicopathological and pathological response. CONCLUSION: NCT alone achieves good tumour response rates in patients with low- and intermediate-risk stage II/III rectal cancer, and predicting tumour response to NCT is feasible at an early treatment phase. REGISTRATION NUMBER: NCT03666442 (http://www.clinicaltrials.gov).

Predicting Response to Total Neoadjuvant Treatment (TNT) in Locally Advanced Rectal Cancer Based on Multiparametric Magnetic Resonance Imaging: A Retrospective Study.

PURPOSE: To investigate the potential value of magnetic resonance imaging (MRI) in predicting response relevance to total neoadjuvant treatment (TNT) in locally advanced rectal cancer. METHODS: We analyzed MRI of 71 patients underwent TNT from 2015 to 2017 retrospectively. We categorized the response of TNT as CR (complete response) vs non-CR, and high vs moderate vs low sensitivity. Logistic regression analysis was used to identify the best predictors of response. Diagnostic performance was assessed using receiver operating characteristic curve analysis. RESULTS: Post-ICT (induction chemotherapy) ∆TL (tumor length), post-CRT (concurrent chemoradiotherapy) ∆LNN (the numbers of lymph node metastases), post-CCT (consolidation chemotherapy) ∆SDWI (maximum cross-sectional area of tumor on diffusion-weighted imaging), post-CCT ADCT (the mean apparent diffusion coefficient values of tumor) and post-CCT ∆LNV (volume of lymph node) were the best CR predictors. Post-ICT ∆TL, post-CRT EMVI (extramural vascular invasion) and post-CCT ∆ST2 (S on T2-weight) were the best significant factors for high sensitivity. CONCLUSION: Post-ICT ∆TL may be an early predictor of CR and high sensitivity to TNT. Dynamic analysis based on MRI between baseline and post-CCT could provide the most valuable prediction of CR. The grouping modality of CR vs non-CR may be more suitable for treatment response prediction than high vs moderate vs low sensitivity.

Secretogranin II impairs tumor growth and angiogenesis by promoting degradation of hypoxia-inducible factor-1α in colorectal cancer.

Distant metastasis is a major cause of death in patients with colorectal cancer (CRC) but the management of advanced and metastatic CRC still remains problematic due to the distinct molecular alterations during tumor progression. Tumor angiogenesis is a key step in tumor growth, invasion and metastasis. However, the signaling pathways involved in angiogenesis are poorly understood. The results of the present study showed that secretogranin II (SCG2) was significantly downregulated in malignant CRC tissues, and higher expression of SCG2 was correlated with longer disease-free survival and overall survival of CRC patients. The results of an animal study showed that ectopic expression of SCG2 significantly inhibited CRC tumor growth by disrupting angiogenesis. Furthermore, the inhibition of expression of vascular endothelial growth factor (VEGF) by SCG2 and rescue of VEGF effectively blocked SCG2-induced inhibition of angiogenesis. Investigations into the underlying mechanism suggested that SCG2 promoted degradation of hypoxia-inducible factor (HIF)-1α by interacting with the von Hippel-Lindau tumor suppressor in CRC cells. Blocking of degradation of HIF-1α effectively attenuated the SCG2-mediated decrease in expression of VEGF in CRC cells. Collectively, these results demonstrated that treatment with SCG2 effectively inhibited CRC tumor growth by disrupting the activities of HIF-1α/VEGF, thereby clarifying the anti-tumor and anti-angiogenesis roles of SCG2 in CRC, while providing a novel therapeutic target and a potential prognostic marker of disease progression.

Transperineal core-needle biopsy of a rectal subepithelial lesion guided by endorectal ultrasound after contrast-enhanced ultrasound: A case report.

BACKGROUND: Rectal subepithelial lesions (SELs) are commonly seen in endoscopic examination, generally manifested as bumps with a smooth surface. Precise preoperative diagnoses for rectal SELs are difficult because abnormal tissues are not easily to be obtained by regular endoscopic forceps biopsy. Traditional guidance modalities of preoperative biopsy, including endoscopic ultrasound, computed tomography, and transabdominal ultrasound, are often unsatisfactory. An updated, safe, and effective biopsy guidance method is required. We herein report a new biopsy guidance modality-endorectal ultrasound (ERUS) combined with contrast-enhanced ultrasound (CEUS). CASE SUMMARY: A 32-year-old woman complained of a mass inside the rectovaginal space for 9 years, which became enlarged within 1 year. A rectal SEL detected by endoscopy was suspected to be a gastrointestinal stromal tumor or exophytic uterine fibroid. Pathological diagnosis was difficult because of unsuccessful transabdominal core needle biopsy with insufficient tissues, as well as vaginal hemorrhage. A second biopsy was suggested after multiple disciplinary treatment discussion, which referred to a transperineal core needle biopsy (CNB) guided by ERUS combined with CEUS. Adequate samples were procured and rectal gastrointestinal stromal tumor was proved to be the pathological diagnosis. Imatinib was recommended for first-line therapy by multiple disciplinary treatment discussion. After the tumor shrunk, resection of the rectal gastrointestinal stromal tumor was performed through the posterior vaginal wall. Adjuvant therapy was applied and no recurrence or metastasis has been found by the last follow-up on December 13, 2019. CONCLUSION: Transperineal CNB guided by ERUS and CEUS is a safe and effective preoperative biopsy of rectal SELs yet with some limitations.

Cyclophosphamide loaded thermo-responsive hydrogel system synergize with a hydrogel cancer vaccine to amplify cancer immunotherapy in a prime-boost manner.

Although neoantigen-based cancer vaccines show great potential in cancer immunotherapy due to their ability to induce effective and long-lasting anti-tumor immunity, their development is hindered by the limitations of neoantigens identification, low immunogenicity, and weak immune response. Cyclophosphamide (CTX) not only directly kills tumors but also causes immunogenic cell death, providing a promising source of antigens for cancer vaccines. Herein, a combined immunotherapy strategy based on temperature-sensitive PLEL hydrogel is designed. First, CTX-loaded hydrogel is injected intratumorally into CT26 bearing mice to prime anti-tumor immunity, and then 3 days later, PLEL hydrogels loaded with CpG and tumor lysates are subcutaneously injected into both groins to further promote anti-tumor immune responses. The results confirm that this combined strategy reduces the toxicity of CTX, and produces the cytotoxic T lymphocyte response to effectively inhibit tumor growth, prolong survival, and significantly improve the tumor cure rate. Moreover, a long-lasting immune memory response is observed in the mice. About 90% of the cured mice survive for at least 60 days after being re-inoculated with tumors, and the distant tumor growth is also well inhibited. Hence, this PLEL-based combination therapy may provide a promising reference for the clinical promotion of chemotherapy combined with cancer vaccines.

Recent progress in nanoformulations of cabazitaxel.

The antitumor efficacy of various paclitaxel (PTX) and docetaxel (DTX) formulations in clinical applications is seriously affected by drug resistance. Cabazitaxel, a second-generation taxane, exhibits greater anticancer activity than paclitaxel and docetaxel and has low affinity for the P-glycoprotein (P-gp) efflux pump because of its structure. Therefore, cabazitaxel has the potential to overcome taxane resistance. However, owing to the high systemic toxicity and hydrophobicity of cabazitaxel and the instability of its commercial preparation, Jevtana®, the clinical use of cabazitaxel is restricted to patients with metastatic castration-resistant prostate cancer (mCRPC) who show progression after docetaxel-based chemotherapy. Nanomedicine is expected to overcome the limitations associated with cabazitaxel application and surmount taxane resistance. This review outlines the drug delivery systems of cabazitaxel published in recent years, summarizes the challenges faced in the development of cabazitaxel nanoformulations, and proposes strategies to overcome these challenges.

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

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

Clinical characteristics and prognostic factors of colorectal cancer patients with ovarian metastasis: a multicenter retrospective study.

PURPOSE: As a kind of secondary tumor of the ovary, ovarian metastasis from colorectal cancer (OMCRC) happens rarely. Prognostic factors of OMCRC are still undetermined. This study was conducted to analyze clinical characteristics and prognostic factors of OMCRC patients. METHODS: Data of patients with OMCRC were collected retrospectively from four large-capacity hospitals in China. Kaplan-Meier method was applied to estimate disease-specific overall survival (OS), and multivariate Cox regression analysis was used to identify prognostic factors. A novel nomogram was developed to estimate individual survival probability, whose performance was internally validated using concordance index (C-index) and calibration curve. RESULTS: Totally, 162 cases were eligible, with a median age at diagnosis of 49 years old. The median size of ovarian metastases was 9.0 cm (95% CI: 8.5-10.4 cm). 93.8% of patients received surgery of ovarian metastases. Median time from CRC diagnosis to metachronous ovarian metastasis was 13.0 months (95% CI: 13.5-17.7 months). Median OS after ovarian metastasis diagnosis was 26.0 months (95% CI: 22.3-29.7 months). Integrating univariate and multivariate analyses, eight factors (including age, menopausal status, primary tumor location, N stage of primary tumor, surgery of primary tumor, differentiation grade, bilateral metastasis, and systemic chemotherapy) were used to develop a novel nomogram, with a C-index of 0.65 (95% CI: 0.595-0.705). Calibration curves indicated relatively good agreement between predicted and actual survival. CONCLUSIONS: This nomogram could be a promising tool to help clinicians to estimate individual survival outcome of patients with OMCRC. Further study is warranted to validate the practicality of this model.

Lateral lymph node dissection reduces local recurrence of locally advanced lower rectal cancer in the absence of preoperative neoadjuvant chemoradiotherapy: a systematic review and meta-analysis.

BACKGROUND: The impact of lateral lymph node dissection (LLND) in locally advanced lower rectal cancer remains controversial. This study is to compare total mesorectal excision (TME) with or without LLND in lower rectal cancer cases of stage II/III. METHODS: The electronic databases were systematically searched that compared TME with or without LLND among patients with lower rectal cancer in clinical stage II/III. Subgroup analysis was performed considering neoadjuvant chemoradiotherapy (nCRT). The hazard ratios (HR), relative risk (RR), and weighted mean difference (WMD) were pooled. RESULTS: Twelve studies of 4458 patients of this meta-analysis demonstrate, LLND alone significantly reduced the local recurrence rate of patients who did not receive nCRT (RR 0.71, P = 0.004), while the difference was not significant when combined with nCRT (RR 0.70, P = 0.36). The analysis shows TME with LLND was associated with significantly longer operation time (WMD 90.73 min, P < 0.001), more intraoperative blood loss (WMD 303.20 mL, P < 0.001), and postoperative complications (RR = 1.35, P =0.02). Whereas urinary dysfunction (RR 1.44, P = 0.38), sexual dysfunction (RR 1.41, P = 0.17), and postoperative mortality (RR = 1.52, P = 0.70), were similar between these two groups. Statistically, no significant differences were observed in OS (HR 0.93, P = 0.62), DFS (HR 0.99, P = 0.96), total recurrence (RR 0.98, P = 0.83), lateral recurrence (RR 0.49, P = 0.14), or distal recurrence (RR 0.95, P = 0.78) between these two groups regardless of whether nCRT was performed or not. CONCLUSIONS: The study shows LLND alone decreases the local recurrence without using nCRT irrespective of the survival advantage in locally advanced lower rectal cancer. The benefit of controlling local recurrence by LLND alone makes us reconsider the usage of nCRT with LLND. TRIAL REGISTRATION: The protocol for this meta-analysis was registered prospectively with PROSPERO ( CRD42020135575 ) on 16 May 2019.