Background
Advanced low rectal cancer has a non-negligible risk of lateral pelvic lymph node (LPLN) metastasis (LPLNM) and lateral local recurrence (LR) after neoadjuvant (chemo)radiotherapy and ...total mesorectal excision. LPLN dissection (LPLND) reduces LR but increases postoperative complications and sexual/urinary dysfunction.
Objective
The aim of this study was to develop a new radiomics-based prediction model for LPLNM in patients with rectal cancer.
Methods
A total of 247 patients with rectal cancer and enlarged LPLNs treated by (chemo)radiotherapy and LPLND were enrolled in this retrospective, multicenter study. LPLN radiomic features were extracted from pretreatment portal venous-phase computed tomography images. A radiomics score of LPLN was constructed based on the least absolute shrinkage and selection operator regression in a primary cohort of 175 patients. Model performance was assessed in terms of discrimination, calibration, and decision curve analysis, and was externally validated in 72 patients.
Results
The radiomics score showed significantly better discrimination compared with pretreatment short-axis diameter measurements in both the primary (area under the curve AUC 0.91 vs. 0.83,
p
= 0.0015) and validation (AUC 0.90 vs. 0.80,
p
= 0.0298) cohorts. Decision curve analysis also indicated the superiority of the radiomics score. In a subanalysis of patients with a short-axis diameter ≥ 7 mm, the radiomics nomogram, incorporating the radiomics score and LPLN shrinkage to ≤ 4 mm, had better discrimination compared with a model incorporating only LPLN shrinkage in both cohorts.
Conclusions
Radiomics-based prediction modeling provides individualized risk estimation of LPLNM in rectal cancer patients treated with (chemo)radiotherapy, and outperforms measurements of pretreatment LPLN diameter.
Non-minimal two-loop inflation Inagaki, Tomohiro; Nakanishi, Ryota; Odintsov, Sergei D.
Physics letters. B,
05/2015, Letnik:
745
Journal Article
Recenzirano
Odprti dostop
We investigate the chaotic inflationary model using the two-loop effective potential of a self-interacting scalar field theory in curved spacetime. We use the potential which contains a non-minimal ...scalar curvature coupling and a quartic scalar self-interaction and which was found in Ref. 1. We analyze the Lyapunov stability of de Sitter solution and show the stability bound. Calculating the inflationary parameters, we systematically explore the spectral index ns and the tensor-to-scalar ratio r, with varying the four parameters, the scalar-curvature coupling ξ0, the scalar quartic coupling λ0, the renormalization scale μ and the e-folding number N. It is found that the two-loop correction on ns is much larger than the leading-log correction, which has previously been studied in Ref. 2. We show that the model is consistent with the observation by Planck with WMAP 3,4 and a recent joint analysis of BICEP2 5.
Background
CD44 variant 9 (CD44v9) has been reported to suppress reactive oxygen spices (ROS) in association with antioxidant factors such as glutathione (GSH) and glutathione peroxidase 2 (GPx2), ...resulting in promoted tumor growth.
Methods
CD44v9 and GPx2 expression were investigated by immunohistochemistry in resected specimens from 193 gastric cancer (GC) patients without preoperative chemotherapy and in pretreatment biopsy specimens from 29 GC patients with preoperative chemotherapy. We analyzed the relationship between CD44v9 expression and clinicopathological factors, prognosis, and pathological response to chemotherapy. In GC cell lines, we examined the relationship between CD44v9 expression and chemotherapeutic sensitivity.
Results
In patients without preoperative chemotherapy, CD44v9 expression was significantly associated with depth of invasion, lymphatic permeation, vascular invasion, distant metastasis and GPx2 expression. In multivariate analysis, CD44v9 expression was an independent poor prognosis factor for overall survival and recurrence-free survival. In patients with preoperative chemotherapy, CD44v9 expression was significantly associated with worse pathological response and GPx2 expression. In GC cell lines, downregulation of CD44v9 expression enhanced chemotherapeutic sensitivity to 5-fluorouracil with changing GSH and ROS levels.
Conclusions
CD44v9-positive expression was associated with chemotherapeutic resistance by controlling intracellular accumulated ROS, suggesting that CD44v9 may be a predictive biomarker for chemotherapy in GC.
Signal regulatory protein alpha (SIRPα) is a type I transmembrane protein that inhibits macrophage phagocytosis of tumor cells upon interaction with CD47, and the CD47‐SIRPα pathway acts as an immune ...checkpoint factor in cancers. This study aims to clarify the clinical significance of SIRPα expression in esophageal squamous cell carcinoma (ESCC). First, we assessed SIRPα expression using RNA sequencing data of 95 ESCC tissues from The Cancer Genome Atlas (TCGA) and immunohistochemical analytic data from our cohort of 131 patients with ESCC. Next, we investigated the correlation of SIRPα expression with clinicopathological factors, patient survival, infiltration of tumor immune cells, and expression of programmed cell death‐ligand 1 (PD‐L1). Overall survival was significantly poorer with high SIRPα expression than with low expression in both TCGA and our patient cohort (P < .001 and P = .027, respectively). High SIRPα expression was associated with greater depth of tumor invasion (P = .0017). Expression of SIRPα was also significantly correlated with the tumor infiltration of M1 macrophages, M2 macrophages, CD8+ T cells, and PD‐L1 expression (P < .001, P < .001, P = .03, and P < .001, respectively). Moreover, patients with SIRPα/PD‐L1 coexpression tended to have a worse prognosis than patients with expression of either protein alone or neither. Taken together, SIRPα indicates poor prognosis in ESCC, possibly through inhibiting macrophage phagocytosis of tumor cells and inducing suppression of antitumor immunity. Signal regulatory protein alpha should be considered as a potential therapeutic target in ESCC, especially if combined with PD‐1‐PD‐L1 blockade.
This article highlights the clinical significance of signal regulatory protein alpha (SIRPα) in esophageal squamous cell carcinoma (ESCC). The results showed that high SIRPα expression was a significant indicator of poor prognosis in ESCC and SIRPα/programmed cell death‐ligand 1 (PD‐L1) coexpression had a negative synergistic impact on prognosis in ESCC. Thus, SIRPα could be a novel clinical biomarker and a potential therapeutic target in ESCC, especially if combined with PD‐1‐PD‐L1 blockade.
Background
Acquiring appropriate laparoscopic technique is necessary to safely perform laparoscopic surgery. The Endoscopic Surgical Skill Qualification System of the Japanese Society of Endoscopic ...Surgery, which was established to improve the quality of laparoscopic surgery in Japan, provides training to become an expert laparoscopic surgeon. In this study, we describe our educational system, in a Japanese highest volume cancer center, and evaluate the system according to the pass rate for the Endoscopic Surgical Skill Qualification System examination.
Methods
We assessed 14 residents who trained for more than 2 years from 2012 to 2018 in our department. All teaching surgeons, qualified by the Endoscopic Surgical Skill Qualification System, participated in all surgeries as supervisors. For the first 3 months, trainees learned as the scopist, then as the first assistant for 3 months, and then by performing laparoscopic surgery as an operator during ileocecal resection or sigmoidectomy. Trainees apply for this training in their second year of residency or later. All laparoscopic procedures in our department are standardized in detail.
Results
The cumulative pass rate was 75% (12/16), and 87% (12/14) of the trainees eventually passed, while the general pass rate was approximately 30%. On average, those who passed in their second or third year had experienced 94 procedures as the surgeon, 177 as the first assistant, and 199 as the scopist. The number of laparoscopic procedures and the learning curves did not differ between successful and failed applicants.
Conclusions
Through our educational system, residents successfully acquired laparoscopic skills with a much higher pass rate in the Endoscopic Surgical Skill Qualification System examination than the general standard. Laparoscopic practice under supervision by experienced surgeons with standardized procedures and accurate understanding of the relevant anatomy is very helpful to achieving appropriate laparoscopic technique.
Purpose
The significance of sarcopenia after colorectal cancer (CRC) resection has only been discussed with relatively small samples or short follow-up periods. This study aimed to clarify the ...clinical significance of sarcopenia in a large-sample study.
Methods
We retrospectively analyzed the relationship between sarcopenia and clinical factors, surgical outcomes, and the survival in 494 patients who underwent CRC surgery between 2004 and 2013. Sarcopenia was defined based on the sex-specific skeletal muscle mass index measured by preoperative computed tomography.
Results
Sarcopenia was associated with sex (higher rate of male,
P
< 0.0001), and low body mass index (
P
< 0.0001), but not age or tumor stage. Sarcopenia was associated with higher incidence of all postoperative complications (
P
= 0.02), especially for patients with Clavien–Dindo classification grade ≥2 (CDC;
P
= 0.0007). Postoperative hospital stays were significantly longer for sarcopenic patients than for non-sarcopenic patients (
P
= 0.02). In a multivariate analysis, sarcopenia was an independent predictor for postoperative complications (
P
= 0.01, odds ratio 1.82, 95% confidence interval 1.13–3.00). Among postoperative complications (CDC grade ≥2), sarcopenia was correlated with non-surgical-site infections (
P
= 0.03). Sarcopenia was not correlated with the overall or recurrence-free survival.
Conclusions
Sarcopenia was an independent predictive factor for postoperative complications after CRC surgery.
Objective
The aim of this study was to develop a radiomics-based prediction model for the response of colorectal liver metastases to oxaliplatin-based chemotherapy.
Methods
Forty-two consecutive ...patients treated with oxaliplatin-based first-line chemotherapy for colorectal liver metastasis at our institution from August 2013 to October 2019 were enrolled in this retrospective study. Overall, 126 liver metastases were chronologically divided into the training (
n
= 94) and validation (
n
= 32) cohorts. Regions of interest were manually segmented, and the best response to chemotherapy was decided based on Response Evaluation Criteria in Solid Tumors (RECIST). Patients who achieved clinical complete and partial response according to RECIST were defined as good responders. Radiomics features were extracted from the pretreatment enhanced computed tomography scans, and a radiomics score was calculated using the least absolute shrinkage and selection operator regression model in a trial cohort.
Results
The radiomics score significantly discriminated good responders in both the trial (area under the curve AUC 0.8512, 95% confidence interval CI 0.7719–0.9305;
p
< 0.0001) and validation (AUC 0.7792, 95% CI 0.6176–0.9407;
p
< 0.0001) cohorts. Multivariate analysis revealed that high radiomics scores greater than − 0.06 (odds ratio OR 23.803, 95% CI 8.432–80.432;
p
< 0.0001), clinical non-T4 (OR 6.054, 95% CI 2.164–18.394;
p
= 0.0005), and metachronous disease (OR 11.787, 95% CI 2.333–70.833;
p
= 0.0025) were independently associated with good response.
Conclusions
Radiomics signatures may be a potential biomarker for the early prediction of chemosensitivity in colorectal liver metastases. This approach may support the treatment strategy for colorectal liver metastasis.
Tubulin-binding agents (TBAs) are designed to target microtubule (MT) dynamics, resulting in compromised mitotic spindles and an unsatisfied spindle assembly checkpoint. The activity of Aurora B ...kinase is indispensable for TBA-induced mitotic arrest, and its inhibition causes mitotic slippage and postmitotic endoreduplication. However, the precise phenomenon underlying mitotic slippage, which is caused by treatment with both Aurora B inhibitors and TBAs, and the cell fate after postmitotic slippage are not completely understood. Here, we found that HeLa and breast cancer cells treated with the different types of TBAs, such as paclitaxel and eribulin (MT-stabilizing and MT-destabilizing agents, respectively), exhibited distinct behaviors of mitotic slippage on inhibition of Aurora B. In such conditions, the cell fates after postmitotic slippage vastly differed with respect to cell morphology, cell proliferation, and cytotoxicity in short-term culture; that is, the effects of inhibition of Aurora B were beneficial for cytotoxicity enhancement in eribulin treatment but not in paclitaxel. However, in long-term culture, the cells that survived after mitotic slippage underwent endoreduplication and became giant cells in both cases, resulting in cellular senescence. We propose that MT-destabilizing agents may be more appropriate than MT-stabilizing agents for treating cancer cells with a weakened Aurora B kinase activity.
Background
The purpose of this study was to clarify the effect of preoperative chemoradiotherapy (CRT) for esophageal cancer on the postoperative course, and to determine the clinical significance of ...salvage esophagectomy after definitive CRT.
Methods
Based on their preoperative treatment, 477 patients with esophageal cancer were classified into three groups: 253 patients who received surgery alone (Group I), 197 who received planned CRT (30–45 Gy, Group II), and 27 who received a salvage esophagectomy (radiation ≥60 Gy, Group III).
Results
Postoperative complications developed in 25, 40, and 59% of the patients in Groups I, II, and III, respectively, with pulmonary complications developing in 10, 15, and 30%, and anastomotic leakage developing in 13, 23, and 37%, respectively. Mortality rates were 2.4, 2.0, and 7.4%, respectively. Multivariate analysis revealed preoperative therapy to be an independent factor associated with postoperative risks: the odds ratios (ORs) of Groups II and III compared to Group I were 1.8 and 4.0 for pulmonary complications, while they were 1.9 and 2.8, respectively, for anastomotic leakage. No critical complications developed in the 14 patients who received salvage surgery performed with strict surgical indications after 2005. The survival of Group III was not significantly different from that of Groups I and II. Most patients who received an R1/R2 resection after definitive CRT died within 2 years after salvage surgery.
Conclusions
Preoperative CRT is associated with postoperative complications especially in patients with R2 resection, while long-term survival can be achieved after R0 resections. Salvage surgery should be considered for carefully selected patients in whom R0 resection can be achieved.
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