A 68-year-old man underwent adjuvant radioiodine therapy for follicular variant papillary thyroid carcinoma. Post-therapeutic whole-body I-131 scan showed abnormal radioiodine uptake on the right side of back. SPECT/CT localized this abnormal activity from a small subcutaneous lesion with fat density between the right 10th and 11th rib. Under ultrasound-guided autopsy, the lesion was confirmed as lipoma.
Thoracoscopic intrathoracic esophagogastrostomy is a technically demanding operation; these technical requirements restrict the extensive application of minimally invasive Ivor Lewis esophagectomy. In an attempt to reduce the difficulty of this surgical procedure, we developed a modified anastomotic technique for thoracolaparoscopic Ivor Lewis esophagectomy. During the entirety of this modified approach, neither technically challenging operations such as intrathoracic suturing, or knotting, nor special instruments such as an OrVil system or a reversepuncture head are required. Between Octomber 2015 and January 2016, 15 consecutive patients with cancer in the distal third of the esophagus or the gastric cardia underwent this modified surgical procedure. The good short- term outcomes that were achieved suggest that the modified anastomotic technique is safe and feasible for thoracolaparoscopic Ivor Lewis esophagectomy.
Deferoxamine (DFO), an iron chelator, is commonly used to remove excess iron from the body. DFO has also been demonstrated to have anti-tumor effect. However, there is no available report on the effect of deferoxamine on mesenchymal stromal cells (MSCs). In this study, we first isolated tumor-associated MSCs (TAMSCs) from EG-7 tumors, which were positive for CD29, CD44, CD73, CD90 and CD105. Ex vivo cultured stem cells derived from tumor and bone marrow compartment were exposed to DFO. We demonstrated that DFO had growth-arresting and apoptosis-inducing effect on TAMSCs and bone marrow MSCs (BMMSCs). DFO also influenced the expression pattern of adhesion molecule VCAM-1 on both TAMSCs and BMMSCs. Notwithstanding its widespread use, our results here warrants caution in the application of DFO, and also highlights the need for careful evaluation of the bone marrow compartment in patients receiving DFO treatment. (C) 2016 Elsevier B.V. All rights reserved.
Acute pancreatitis (AP) is a rare manifestation of pancreatic cancer (PC). The relationship between AP and PC remains less distinct. From January 2009 to November 2015, 47consecutive patients with PC who presented with AP were reviewed for this study. Clinical features, clinicopathologic variables, postoperative complications, and follow-up evaluations of patients were documented in detail from our database. In order to identify cutoff threshold time for surgery, receiver operating curve (ROC) was built according to patients with or without postoperative complications. Cumulative rate of survival was calculated by using the Kaplan-Meier method. The study was conducted in accordance with the principles of the Declaration of Helsinki and the guidelines of West China Hospital. This study included 35 men (74.5%) and 12 women (25.5%) (mean age: 52 years), with a median follow-up of 40 months. AP was clinically mild in 45 (95.7%) and severe in 2 (4.3%). The diagnosis of PC was delayed by 2 to 660 days (median 101 days). Thirty-nine (83.0%) cases underwent surgery. Eight (17.0%) cases performed biopsies only. Of 39 patients, radical surgery was performed in 32 (82.1%) cases and palliative in 7 (19.9%) cases. Two (8.0%) patients were needed for vascular resection and reconstruction. Postoperative complications occurred in 12 (30.8%) patients. About 24.5 days was the best cutoff point, with an area under curve (AUC) of 0.727 (P=0.025, 95% confidence interval: 0.555-0.8999). The survival rate of patients at 1 year was 23.4%. The median survival in patients with vascular resection and reconstruction was 18 months, compared with 10 months in patients without vascular resection (P=0.042). For the primary stage (T), Tix was identified in 3 patients, the survival of whom were 5, 28, 50 months, respectively. And 2 of them were still alive at the follow-up period. The severity of AP was mainly mild. Surgical intervention after 24.5 days may benefit for reducing postoperative complications. Patients with vascular resection and reconstruction, thus achieving tumor-free margins, had a long-time survival.
Objectives: To identify the associations of lymph node metastases (pN+), number of positive nodes, and pN subclassification with cancer, treatment, patient, geographic, and institutional variables, and to recommend extent of lymphadenectomy needed to accurately detect pN+ for esophageal cancer. Summary Background Data: Limited data and traditional analytic techniques have precluded identifying intricate associations of pN+ with other cancer, treatment, and patient characteristics. Methods: Data on 5806 esophagectomy patients from the Worldwide Esophageal Cancer Collaboration were analyzed by Random Forest machine learning techniques. Results: pN+, number of positive nodes, and pN subclassification were associated with increasing depth of cancer invasion (pT), increasing cancer length, decreasing cancer differentiation (G), and more regional lymph nodes resected. Lymphadenectomy necessary to accurately detect pN+ is 60 for shorter, well-differentiated cancers (<2.5 cm) and 20 for longer, poorly differentiated ones. Conclusions: In esophageal cancer, pN+, increasing number of positive nodes, and increasing pN classification are associated with deeper invading, longer, and poorly differentiated cancers. Consequently, if the goal of lymphadenectomy is to accurately define pN+ status of such cancers, few nodes need to be removed. Conversely, superficial, shorter, and well-differentiated cancers require a more extensive lymphadenectomy to accurately define pN+ status.
Cancer-associated fibroblasts (CAFs) are one major type of component identified in the tumor microenvironment. Studies have focused on the genetic and epigenetic status of CAFs, since they are critical in tumor progression and differ phenotypically and functionally from normal fibroblasts. The present review summarizes the recent achievements in understanding the gene profiles of CAFs and pays special attention to their possible epigenetic alterations. A total of 7 possible genetic alterations and epigenetic changes in CAFs are discussed, including gene differential expression, karyotype analysis, gene copy number variation, loss of heterozygosis, allelic imbalance, microsatellite instability, post-transcriptional control and DNA methylation. These genetic and epigenetic characteristics are hypothesized to provide a deep understanding of CAFs and a perspective on their clinical significance.
The influence of the biological relationship between the donor and the recipient is rarely discussed in living donor liver transplantation (LDLT), although it is believed to be an important risk factor in other types of organ transplantations. A total of 272 consecutive patients undergoing adult to adult right lobe LDLT were retrospectively analyzed and stratified into a nonbiologically related (NBR) group (69 patients) and a biologically related (BR) group (203 patients). The preoperative data and postoperative outcomes of both recipients and donors were evaluated. More than two-thirds of the recipients had histories of HBV infection, and hepatocellular carcinoma (HCC) was the main reason for the patients undergoing LDLT in both groups. The percentage of female donors in the NBR group was more than the percentage in the BR group (P=0.000). There were no differences between the groups in postoperative laboratory testing or daily immunosuppression dose, and the complication rates in both the recipient and donor surgeries showed no significant differences. For patients with benign diseases, the cumulative 1-, 3-, 5-, and 10-year survival rate were 92.9% in the 4 periods in the NBR group and 89.1%, 87.6%, 83.7%, and 83.7%, respectively, in BR group, while for the patients diagnosed as HCC, if patients exceeding the Milan criteria were involved, the 5-year survival rate was 41.2%, compared to 82% for patients within the Milan criteria, which was nearly the same as for those with the benign disease. In conclusion, our findings suggested that the biological relationship between the donor and the recipient in adult to adult LDLT was not associated with the short-and long-term outcomes of recipients diagnosed with benign liver diseases and early stage HCC. Moreover, the criteria for patients diagnosed with HCC to undergo LDLT should be restrictively selected.
Interleukin 23 (IL-23) is an inflammatory cytokine which plays a vital role in autoimmune diseases as well as in tumorigenesis. However, the role of IL-23 in tumor procession is still controversial and the underlying mechanism remains unclear. Here we established a stable cell line overexpressing IL-23 to prove that IL-23 promoted tumor growth and pulmonary metastasis through induction of tumor-related inflammation and absence of immune surveillance. IL-23 promotes tumor-associate inflammatory response such as infiltration of M2 macrophages, neutrophils and their elevated secretions of immunosuppressive cytolcines transforming growth factor-beta (TGF-beta), IL-10 and vascular endothelial growth factor (VEGF) into tumor tissues, meanwhile the increase of the matrix metalloprotease MMP9. In addition, IL-23 increases the expression of the endothelial marker CD31 and proliferative marker Ki67 in tumors. Moreover, IL23 induces immunosuppression though reducing the infiltration of CD4(+) and CD8(+)T cells into tumor tissues. In conclusion, IL-23 is a considerable molecular in tumor progression, which simultaneously facilitates processes of pro-tumor inflammation, such as angiogenesis, immunosuppressive cytolcines as well as infiltrations of M2 macrophages and neutrophils, and suppresses antitumor immune responses through reduction of CD4(+) T cells and CD8(+) T cells. (C) 2016 Elsevier Inc. All rights reserved.
Purpose Long non-coding RNAs (lncRNAs) play important roles in the malignant behavior of cancer. HOTAIR, a well-studied lncRNA, contributes to breast cancer development, and overexpression of HOTAIR predicts a poor prognosis. However, the regulatory role of HOTAIR in the cancer stem-like cell (CSC) subpopulation remains largely unknown. Our goal was to determine the regulatory functions of HOTAIR in the processes of self-renewal capacity, tumor formation and proliferation of CSCs derived from breast cancer. Methods We first enriched and incubated the CSC population derived from breast cancer cell line MCF7 (CSC-MCF7) or MDA-MB-231 (MB231, CSC-MB231). Self-renewal capacity and tumor formation were assessed in vitro and in vivo to determine the stemness of CSCs. We assessed the impact on ectopically upregulated or downregulated expression of HOTAIR in CSCs by soft agar, self-renewal capacity and CCK-8 assays. The functional domain of HOTAIR was determined by truncation. RT-qPCR and semiquantitative Western blotting were performed to detect the expression levels of genes of interest. Chromatin IP (ChIP) was employed to detect the transcriptional regulatory activity of p53 on its target gene. Results After the identification of CSC properties, RT-qPCR analysis revealed that HOTAIR, but not other cancer-associated lncRNAs, is highly upregulated in both CSC-MCF7 and CSCMB231 populations compared with MCF7 and MB231 populations. By modulating the level of HOTAIR expression, we showed that HOTAIR tightly regulates the proliferation, colony formation, migration and self-renewal capacity of CSCs. Moreover, full-length HOTAIR transcriptionally inhibits miR-34a specifically, leading to upregulation of Sox2, which is targeted by miR-34a. Ectopic introduction of miR-34a mimics reverses the effects of HOTAIR on the physiological processes of CSCs, indicating that HOTAIR affects these processes, including self-renewal capacity; these effects are dependent on the regulation of Sox2 via miR-34a. Interestingly, tight transcriptional regulation of p53 by HOTAIR was found; accordingly, p21 is indirectly regulated by HOTAIR, resulting in cell cycle entry. Conclusion These results suggest that HOTAIR is a key regulator of proliferation, colony formation, invasion and self-renewal capacity in breast CSCs, which occurs in part through regulation of Sox2 and p53.
Background: Multiple studies have reported evidence of an inverse association between parity and bladder cancer risk. However, a comprehensive and quantitative assessment of this association has never been conducted. We conducted this study to clarify this issue. Methods: Systematic search of PubMed and Embase was performed to identify all the studies. Studies were selected based on strict screening with inclusion and exclusion criteria. Summary relative risks (RR) with 95% confidence intervals (CI) were calculated by using a fixed-effect model, and the generalized least squares trend estimation was employed to compute study-specific RR and 95% CI per live birth increase. Heterogeneity and publication bias were also evaluated. Results: Twelve studies (6,214 cases and 2,693,350 non-cases) were eligible in this meta-analysis. The pooled RR of bladder cancer for parous versus nulliparous women was 0.76 (95% CI: 0.70-0.82). Results were similar in the studies that adjusted for BMI(RR = 0.66; 95% CI: 0.53-0.81), cigarette smoking (RR = 0.67; 95% CI: 0.57-0.79), and age (RR = 0.77; 95% CI: 0.71-0.84). The dose-response meta-analysis showed a lower bladder cancer risk (RR = 0.95; 95% CI: 0.92-0.98) for each live birth increase in parous women. No evidence of publication bias or significant heterogeneity was detected in the above-mentioned analyses. Conclusions: The finding from current meta-analysis suggest that parity may be related to decreased risk of bladder cancer.