Programmed death ligand-1/programmed death-1 inhibition therapy and programmed death ligand-1 expression in urothelial bladder carcinoma.

After two decades of unchanged paradigms, the treatment strategies for advanced urothelial bladder cancer have been revolutionized by emerging programmed death ligand-1 (PD-L1)/programmed death-1 (PD1) inhibition therapy. Increased evidence is demonstrating the efficacy of PD-L1/PD1 inhibition therapy in both second-line and first-line settings. However, the percentage of patients who benefit from anti-PD-L1/anti-PD1 therapy is still low. Many questions have been raised in the development of biomarker-driven approaches for disease classification and patient selection. In this perspective, we discuss PD-L1/PD1 expression in urothelial bladder carcinoma, review approved anti-PD-L1/anti-PD1 agents for bladder cancer treatment and current ongoing studies investigating combination treatment strategies, and explore PD-L1 expression status for the evaluation of bladder cancer immunotherapy.

Risk Factors for the Occurrence of Insufficient Cement Distribution in the Fractured Area after Percutaneous Vertebroplasty in Osteoporotic Vertebral Compression Fractures.

BACKGROUND: Insufficient cement distribution (ICD) in the fractured area has been advocated to be responsible for unsatisfied pain relief after percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fractures (OVCFs). However, little is known about risk factors for the occurrence of ICD. OBJECTIVE: The present study aimed to identify independent risk factors of the emergence of ICD. STUDY DESIGN: A retrospective cohort study. SETTING: Department of spinal surgery, an affiliated hospital of a medical university. METHODS: Patients who underwent PVP for single-level OVCF from January 2012 to September 2014 and met this study's inclusion criteria were retrospectively reviewed. Associations of ICD with co-variates (age, gender, bone mass density with a T-score, amount of injected cement, cement leakage, fracture level, fracture age, fracture severity grade, and location of the fractured area) and the influence of ICD on pain relief were analyzed. RESULTS: A total of 225 patients were included. ICD was found in 26 (11.6%) patients. Fractured area located in the superior portion of the index vertebra was significantly associated with occurrence of ICD. No further significant associations between the studied co-variates and emergence of ICD were seen in the adjusted analysis. In addition, patients with ICD had significantly higher immediate postoperative visual analog scale scores of back pain compared with those with sufficient cement distribution in the fractured area. LIMITATION: Location of the fractured area and cement distribution in the fractured area could not be evaluated quantitatively. CONCLUSIONS: The incidence of ICD is higher in patients with the fractured area located in the superior portion of the index vertebra and ICD might be responsible for unsatisfied pain relief after PVP for OVCFs. KEY WORDS: Percutaneous vertebroplasty, insufficient cement distribution, fractured area, risk factor, osteoporosis, vertebral compression fracture, spine, unsatisfied pain relief, cement augmentation.

Management of centrally located hepatocellular carcinoma: Update 2016.

Centrally located hepatocellular carcinoma (HCC) is sited in the central part of the liver and adjacent to main hepatic vascular structures. This special location is associated with an increase in the difficulty of surgery, aggregation of the recurrence disease, and greater challenge in disease management. This review summarizes the evolution of our understanding for centrally located HCC and discusses the development of treatment strategies, surgical approaches and recurrence prevention methods. To improve patient survival, a multi-disciplinary modality is greatly needed throughout the whole treatment period.

Experiment Research on Hot-Rolling Processing of Nonsmooth Pit Surface.

In order to achieve the nonsmooth surface drag reduction structure on the inner polymer coating of oil and gas pipelines and improve the efficiency of pipeline transport, a structural model of the machining robot on the pipe inner coating is established. Based on machining robot, an experimental technique is applied to research embossing and coating problems of rolling-head, and then the molding process rules under different conditions of rolling temperatures speeds and depth are analyzed. Also, an orthogonal experiment analysis method is employed to analyze the different effects of hot-rolling process apparatus on the embossed pits morphology and quality of rolling. The results also reveal that elevating the rolling temperature or decreasing the rolling speed can also improve the pit structure replication rates of the polymer coating surface, and the rolling feed has little effect on replication rates. After the rolling-head separates from the polymer coating, phenomenon of rebounding and refluxing of the polymer coating occurs, which is the reason of inability of the process. A continuous hot-rolling method for processing is used in the robot and the hot-rolling process of the processing apparatus is put in a dynamics analysis.

Myeloid-derived suppressor cells mediate immune suppression in spinal cord injury.

Spinal cord injury (SCI) is characterized by the loss of motor and sensory functions in areas below the level of the lesion and numerous accompanying deficits. Previous studies have suggested that myeloid-derived suppressor cell (MDSC)-induced immune depression may play a pivotal role in the course of SCI. However, the concrete mechanism of these changes regarding immune suppression remains unknown. Here, we created an SCI mouse model to gain further evidence regarding the relationship between MDSCs following SCI and T lymphocyte suppression. We showed that in the SCI mouse model, the expanding MDSCs have the capacity to suppress T cell proliferation, and this suppression could be reversed by blocking the arginase.

Prognostic Factors and Clinical Characteristics for Hepatocellular Carcinoma Patients with Benign Enlarged Perihepatic Lymph Nodes: a Single-Center Experience from China.

BACKGROUND: The clinical and prognostic significance of benign perihepatic lymph nodes enlargement (PLNE) from patients with hepatocellular carcinoma (HCC) remains unclear. The objective of this study is to evaluate the relative frequency, incidence and locations of benign PLNE, and the impact on long-term survival of the patients. METHODS: A total of 219 consecutive patients who underwent curative resection of HCC between July 2006 and March 2012 in our single institution were divided into two groups according to the presence of PLNE: PLNE group (n = 76), and control group (n = 143). The long-term outcomes were evaluated and compared between the two groups. RESULTS: The 1-, 3-, and 5-year recurrence-free survival rates were 77.2, 60.0, and 38.1 % in the PLNE group and 71.3, 42.5, and 25.0 % in the control group (p = 0.080). Corresponding overall survival rates were 96.0, 84.8, 67.1 % and 93.5, 72.4, 46.9 % respectively (p = 0.041). Patients with benign PLNE were associated with a higher rate of centrally located HCCs or tumors adjacent to the major branch of vascular vessels. Multivariate analysis revealed that benign PLNE was an independent positive prognostic factor affecting the overall survival. CONCLUSIONS: According to our analysis, patients of HCC with benign PLNE after curative resection can be expected to have better long-term survival. It is also associated with a lower risk of tumor recurrence, but not significant. This finding may provide new insights into daily clinical practice and the pathophysiological characteristics of HCC development.

Hepatocellular adenoma with malignant transformation in male patients with non-cirrhotic livers.

INTRODUCTION: Hepatocellular adenomas (HCAs), with a risk of malignant transformation into hepatocellular carcinoma (HCC), classically develop in young women who are taking oral contraceptives. It is now clear that HCAs may also occur in men. However, it is rarely reported that HCAs with malignant transformation occur in male patients with non-cirrhotic livers. This study aimed to characterize the malignancy of HCAs occurring in male patients. METHODS: All patients with HCAs with malignant transformation who underwent hepatectomy at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 1, 1999 and December 31, 2011 were enrolled in the study. The clinical characteristics as well as radiologic and pathologic data were reviewed. RESULTS: HCAs with malignant transformation were observed in 5 male patients with non-cirrhotic livers, but not in female patients. The alpha-fetoprotein (AFP) levels were higher in patients with HCAs with malignant transformation than in patients with HCAs without malignant transformation. The diameters of the tumors with malignant transformation were larger than 5 cm in 3 cases and smaller than 5 cm in 2 cases. The 5 patients were all alive without recurrence by the end of the study period. The disease-free survival times of the 5 patients were 26, 48, 69, 69, and 92 months. CONCLUSION: Our results indicate that resection would be advised even if the presumptive diagnosis is adenoma smaller than 5 cm in diameter, especially in male patients.

Three-dimensional morphometric analysis for hepatectomy of centrally located hepatocellular carcinoma: a pilot study.

AIM: To describe a three-dimensional model (3DM) to accurately reconstruct anatomic relationships of centrally located hepatocellular carcinomas (HCCs). METHODS: From March 2013 to July 2014, reconstructions and visual simulations of centrally located HCCs were performed in 39 patients using a 3D subject-based computed tomography (CT) model with custom-developed software. CT images were used for the 3D reconstruction of Couinaud's pedicles and hepatic veins, and the calculation of corresponding tumor territories and hepatic segments was performed using Yorktal DMIT software. The respective volume, surgical margin, and simulated virtual resection of tumors were also estimated by this model preoperatively. All patients were treated surgically and the results were retrospectively assessed. Clinical characteristics, imaging data, procedure variables, pathologic features, and postoperative data were recorded and compared to determine the reliability of the model. RESULTS: 3D reconstruction allowed stereoscopic identification of the spatial relationships between physiologic and pathologic structures, and offered quantifiable liver resection proposals based on individualized liver anatomy. The predicted values were consistent with the actual values for tumor mass volume (82.4 ± 109.1 mL vs 84.1 ± 108.9 mL, P = 0.910), surgical margin (10.1 ± 6.2 mm vs 9.1 ± 5.9 mm, P = 0.488), and maximum tumor diameter (4.61 ± 2.16 cm vs 4.53 ± 2.14 cm, P = 0.871). In addition, the number and extent of portal venous ramifications, as well as their relation to hepatic veins, were visualized. Preoperative planning based on simulated resection facilitated complete resection of large tumors located in the confluence of major vessels. And most of the predicted data were correlated with intraoperative findings. CONCLUSION: This 3DM provides quantitative morphometry of tumor masses and a stereo-relationship with adjacent structures, thus providing a promising technique for the management of centrally located HCCs.

Retrospective evaluation of discrepancies between radiological and pathological size of hepatocellular carcinoma masses.

BACKGROUND: The size of a hepatic neoplasm is critical for staging, prognosis and selection of appropriate treatment. Our study aimed to compare the radiological size of solid hepatocellular carcinoma (HCC) masses on magnetic resonance imaging (MRI) with the pathological size in a Chinese population, and to elucidate discrepancies. MATERIALS AND METHODS: A total of 178 consecutive patients diagnosed with HCC who underwent curative hepatic resection after enhanced MRI between July 2010 and October 2013 were retrospectively identified and analyzed. Pathological data of the whole removed tumors were assessed and differences between radiological and pathological tumor size were identified. All patients were restaged using a modified Tumor-Node-Metastasis (TNM) staging system postoperatively according to the maximum diameter alteration. The lesions were classified as hypo-staged, iso-staged or hyper-staged for qualitative assessment. In the quantitative analysis, the relative pre and postoperative tumor size contrast ratio (%Δsize) was also computed according to size intervals. In addition, the relationship between radiological and pathological tumor diameter variation and histologic grade was analyzed. RESULTS: Pathological examination showed 85 (47.8%) patients were overestimated, 82 (46.1%) patients underestimated, while accurate measurement by MRI was found in 11 (6.2%) patients. Among the total subjects, 14 (7.9%) patients were hypo-staged and 15 (8.4%) were hyper-staged post-operatively. Accuracy of MRI for calculation and characterized staging was related to the lesion size, ranging from 83.1% to 87.4% (<2cm to ≥5cm, p=0.328) and from 62.5% to 89.1% (cT1 to cT4, p=0.006), respectively. Overall, MRI misjudged pathological size by 6.0 mm (p=0.588 ), and the greatest difference was observed in tumors <2cm (3.6 mm, %Δsize=16.9%, p=0.028). No statistically significant difference was observed for moderately differentiated HCC (5.5mm, p=0.781). However, for well differentiated and poorly differentiated cases, radiographic tumor maximum diameter was significantly larger than the pathological maximum diameter by 3.15 mm and underestimated by 4.51 mm, respectively (p=0.034 and 0.020). CONCLUSIONS: A preoperative HCC tumor size measurement using MRI can provide relatively acceptable accuracy but may give rise to discrepancy in tumors in a certain size range or histologic grade. In pathological well differentiated subjects, the pathological tumor size was significantly overestimated, but underestimated in poorly differentiated HCC. The difference between radiological and pathological tumor size was greatest for tumors <2 cm. For some HCC patients, the size difference may have implications for the decision of resection, transplantation, ablation, or arterially directed therapy, and should be considered in staging or selecting the appropriate treatment tactics.

[Comparative study of three types of anatomical vascular occlusion method in hepatectomy for liver neoplasms].

OBJECTIVE: To assess the clinical efficacies of three types of anatomical hepatic inflow occlusion method in hepatectomy for liver neoplasms. METHODS: A non-randomized concurrent controlled trial was performed from January 2011 to October 2012, a total of 180 consecutive patients with liver neoplasms underwent hepatectomy similarly. They were divided into 3 groups according to the hepatic inflow occlusion methods during resection: HHV group (hemi-hepatic vascular inflow occlusion, n = 60), MPV group (main portal vein inflow occlusion, n = 60) and HPP group (hemi-portal vein preserved inflow occlusion, n = 60). The primary endpoints were intraoperative blood loss and transfusion requirement while the secondary outcomes were assessed with operating duration, postoperative morbidity, hospital stay, gastrointestinal function and postoperative liver injury. RESULTS: No significant differences existed among three groups in demographic and tumor characteristics and operation-related background (P > 0.05). No mortality happened in 30 days postoperatively in all patients. Intraoperative volume of blood loss had no significant differences among three groups (P = 0.272). Among the patients requiring transfusion, HPP group had the least transfusion requirement (HHV group: (5.00 ± 1.51) U, MPV group:(3.50 ± 1.41) U, HPP group: (2.50 ± 0.93) U, P = 0.004). MPV group showed a significant shorter operating duration (HHV group: (227 ± 59) min, MPV group:(198 ± 56) min, HPP group:(221 ± 79) min, P = 0.042). No significant differences were found among three groups in hospital stay (P = 0.673) or postoperative morbidity (P = 0.735), including hepatic insufficiency, infection and ascites. HHV group showed an earlier recovery of gastrointestinal function (HHV group: (60 ± 12) h, MPV group:(69 ± 9) h, HPP group:(64 ± 8) h, P = 0.000).MPV group had a significantly lower level of aminotransferase at Day 1 and 3 postoperation (d1 ALT: HHV group: (403 ± 271) U/L, MPV group:(304 ± 211) U/L, HPP group: (448 ± 396) U/L, P = 0.033; d1 AST: HHV group: (394 ± 271) U/L, MPV group:(278 ± 189) U/L, HPP group: (432 ± 405) U/L, P = 0.017; d3 ALT: HHV group: (309 ± 193) U/L, MPV group:(232 ± 161) U/L, HPP group:(325 ± 277) U/L, P = 0.048; d3 AST: HHV group:(136 ± 105) U/L, MPV group:(91 ± 73) U/L, HPP group:(120 ± 87) U/L, P = 0.024).But no significant differences were found among three groups regarding total bilirubin, albumin, prealbumin and prothrombin time activity (P < 0.05) during any postoperative stage. CONCLUSION: All three types of anatomical vascular occlusion method are both safe and efficacious in hepatectomy. But no single method has absolute advantage over the other two. HPP method has the best hemostatic effect, MPV offers better postoperative liver function and HHV promotes early recovery of gastrointestinal function.

[Application of selective and timely regional hepatic vascular occlusion for resection of large centrally located liver tumors: report of 133 cases].

OBJECTIVE: To improve the resection rate and increase operation safety for large centrally located liver tumors. METHODS: Clinical data from 133 patients with large centrally located liver tumors confirmed by surgery were analyzed retrospectively. Selective and timely regional hepatic vascular occlusion was used during the operation procedure. RESULTS: The resection rate was 100%. Perioperative death occurred in one patient. During operations, Forty-four patients underwent regional hepatic inflow occlusion ranging from 12 to 33 minutes. Twenty-three patients underwent left and right inflow occlusion, respectively, ranging from 8 to 50 minutes. One patient had right half-hepatic vascular exclusion for 40 minutes. The blood loss of 132 patients was (665 ± 424) ml (one patient experienced diffuse blood oozing and died in the next day). Among them, the blood loss of patients with liver cirrhosis was (723 ± 479) ml. On the contrary, those without liver cirrhosis was (458 ± 223) ml (P < 0.01). Liver function in 92.4% (122/132) patients recovered to Child-Pugh A within one week. No liver failure occurred. After operation, 3 patients presented ascites. Among them, two patients had liver cirrhosis and hepatocellular jaundice, one patient was accepted for transcatheter arterial chemoembolization preoperatively. Four patients had biliary fistula, one patient had gastroparesis, one patient had thrombus in the superior mesenteric vein and portal vein, and five patients had right pleural effusion. The 1-, 3- and 5-year survival rates of 112 patients were 89.1%, 57.7% and 36.9%, respectively. CONCLUSIONS: Selective and timely regional hepatic vascular occlusion is useful for the resection of large centrally located liver tumors. This kind of procedure can effectively control the blood loss during the operation and shorten the ischemic reperfusion time, beneficial for protecting the liver cell function. This procedure is a safe hepatic flow occlusion method.