Patient-Specific Sarcoma Organoids for Personalized Translational Research: Unification of the Operating Room with Rare Cancer Research and Clinical Implications

Annals of Surgical Oncology - Sarcoma clinical outcomes have been stagnant for decades due to heterogeneity of primaries, lack of comprehensive preclinical models, and rarity of disease. We...     

Efficacy and safety of terlipressin in cirrhotic patients with variceal bleeding or hepatorenal syndrome

Terlipressin is an analog of the natural hormone arginine-vasopressin. It is used in the treatment of patients with cirrhosis and bleeding esophageal varices (BEV) and in patients with hepatorenal syndrome (HRS): two of the most dramatic and feared complications of cirrhosis. Terlipressin exerts its main pharmacological effect through stimulation of vasopressin-1 receptors. These receptors are located in vascular smooth muscle and mediate vasoconstriction. In patients with cirrhosis and portal hypertension, treatment with terlipressin increases mean arterial pressure and decreases portal flow and pressure within minutes of administration. Furthermore, in patients with ascites terlipressin improves glomerular filtration and excretion of sodium. Terlipressin decreases failure of initial hemostasis by 34%, decreases mortality by 34%, and is considered a first-line treatment for BEV, when available. Terlipressin in combination with albumin reverses type 1 HRS in 33%–60% of cases and is the only treatment with proven efficacy in randomized trials. The safety profile is favorable when considering the clinical efficacy and the high mortality of these clinical entities. Adverse events are mostly cardiovascular and related to vasoconstriction. Mortality and withdrawal of terlipressin due to adverse events occurs in less than 1% of cases. Mild adverse events related to terlipressin treatment occur in 10%–20% of patients. The benefit, however, of terlipressin on long-term survival in HRS remains to be determined. At present, treatment with terlipressin and albumin is considered the most efficient therapy and should therefore be recommended for the treatment of type 1 HRS-1.     

Mechanical and Combustion Properties of Agglomerates of Wood of Popular Eastern European Species

The objective of the reported project was to produce wood agglomerates from popular East European species to determine their strength and combustion properties. Closed-die pellets were produced from sawdust of six types of wood common on the East European market: pine, willow, oak, poplar, birch, and beech. The properties of pellets, determined by the type of wood, were influenced by the compaction pressure and the moisture content of the sawdust. The highest average pellet density was obtained for oak sawdust, while the lowest density was obtained for poplar pellets. Expansion of pellets after removing from the die was found to be dependent on the wood species, and as expected, on compaction pressure. The pellet expansion increased after 2 h of conditioning in the laboratory and with an increase in moisture content. The highest and the smallest strength were obtained for oak pellets and for birch sawdust, respectively. The strength of the pellets increased by more than 100% with an increase in the compaction pressure from 60 MPa to 120 MPa. The average strength decreased by 65% with increasing moisture content. For all tested materials, drop resistance remained at a high level, acceptable in industrial practice. The highest calorific value of 18.97 MJ/kg was obtained for pine pellets. The highest ash value of 1.52% was obtained for willow pellets and the lowest value of 0.32% for pine pellets.     

The Influence of Mechanical Alloying and Plastic Consolidation on the Resistance to Arc Erosion of the Ag–Re Composite Contact Material

The article presents the influence of mechanical alloying and plastic consolidation on the resistance to arc erosion of the composite Ag–Re material against the selected contact materials. The following composites were selected for the tests: Ag90Re10, Ag95Re5, Ag99Re1 (bulk chemical composition). Ag–Re materials were made using two methods. In the first, the materials were obtained by mixing powders, pressing, sintering, extrusion, drawing, and die forging, whereas, in the second, the process of mechanical alloying was additionally used. The widely available Ag(SnO₂)10 and AgNi10 contact materials were used as reference materials. The reference AgNi10 material was made by powder metallurgy in the process of mixing, pressing, sintering, extrusion, drawing, and die forging, while the Ag(SnO₂)10 composite was obtained by spraying AgSniBi alloy with water, and then the powder was pressed, oxidized internally, sintered, extruded into wire, and drawn and die forged. The tests of electric arc resistance were carried out for loads with direct current (DC) and alternating current (AC). For alternating current (I = 60 A, U = 230 V), 15,000 switching cycles were made, while, for constant current 50,000 (I = 10 A, U = 550 V). A positive effect of the mechanical alloying process and the addition of a small amount of rhenium (1% by mass) on the spark erosion properties of the Ag–Re contact material was found. When DC current of 10 A was used, AgRe1 composite was found to be more resistant than commonly used contact materials (AgNi10 and Ag(SnO₂)10).     

Status of minimal residual disease after induction predicts outcome in both standard and high-risk Ph-negative adult acute lymphoblastic leukaemia. The Polish Adult Leukemia Group ALL 4-2002 MRD Study

The treatment of adults with Philadelphia-negative acute lymphoblastic leukaemia (ALL) depends on the presence of risk factors including age, white blood cell count, immunophenotype and time to complete remission. In recent years, status of minimal residual disease (MRD) has been postulated as an additional risk criterion. This study prospectively evaluated the significance of MRD. Patients were treated with a uniform Polish Adult Leukemia Group (PALG) 4-2002 protocol. MRD status was assessed after induction and consolidation by multiparametric flow cytometry. Out of 132 patients included (age, 17–60 years), 116 patients were suitable for analysis. MRD level ≥0·1% of bone marrow cells after induction was found to be a strong and independent predictor for relapse in the whole study population ( P  < 0·0001), as well as in the standard risk (SR, P  = 0·0003) and high-risk ( P  = 0·008) groups. The impact of MRD after consolidation on outcome was not significant. The combination of MRD status with conventional risk stratification system identified a subgroup of patients allocated to the SR group with MRD <0·1% after induction who had a very low risk of relapse of 9% at 3 years as opposed to 71% in the remaining subjects ( P  = 0·001). We conclude that MRD evaluation after induction should be considered with conventional risk criteria for treatment decisions in adult ALL.     

The Role of 3-D Endorectal Ultrasound in Rectal Cancer: Our Experience

In the last 20 years, endorectal ultrasound (ERUS) has been one of the main diagnostic methods for locoregional staging of rectal cancer. ERUS is accurate modality for evaluating local invasion of rectal carcinoma into the rectal wall layers (T category). Adding the three-dimensional modality (3-D) increases the capabilities of this diagnostic tool in rectal cancer patients. We review the literature and report our experience in preoperative 3-D ERUS in rectal cancer staging. In the group of 71 patients, the staging of preoperative 3-D endorectal ultrasonography was compared with the postoperative morphologic examination. Three-dimensional ERUS preoperative staging was confirmed with morphologic evaluation in 66 out of 71 cases (92.9%). The detection sensitivities of rectal cancer with 3-D ERUS were as follows: T1, 92.8%; T2, 93.1%; T3, 91.6%; and T4, 100.0%; with specificity values of T1, 98.2%; T2, 95.4%; T3, 97.8%; and T4, 98.5%. Three-dimensional ERUS correctly categorized patients with T1, 97.1%; T2, 94.3%; T3, 95.7%; and T4, 98.5%. The percentage of total overstaged cases was 2.75% and that of understaged cases was 6.87%. The metastatic status of the lymph nodes was determined with a sensitivity of 79.1% (19 of 24), specificity of 91.4% (43 of 47), and diagnostic accuracy of 87.3% (62 of 71). In our experience, 3-D ERUS has the potential to become the diagnostic modality of choice for the preoperative staging of rectal cancer.Key words: Three-dimensional endorectal ultrasound, Rectal cancerEndorectal ultrasound (ERUS) has been used as a diagnostic tool for evaluation and staging of rectal cancer since the 1980s.¹ According to the literature, in studies with more than 50 patients included, an overall accuracy of approximately 81.8% was reported.² Most of the studies present data between 85% and 95%, but in the studies with more than 200 patients, the accuracy rates are relatively lower—63.3% and 69%, respectively.^3,4 A common disadvantage of ERUS and magnetic resonance imaging (MRI) is the overstaging of T2 tumors owing to an irregular outer rectal wall resulting from transmural tumor extension or inflammation around the tumor. Another challenge for the ERUS, and especially the rigid probes, are the locally advanced, stenotic tumors, where the probe may not be able to pass above the lesion.⁵ The nodal staging accuracy of ERUS ranges from 70% to 75%.^1,5,6 The metastatic lymph nodes are distinguished by hypoechoic appearance, round shape, peritumoral location, and size >5 mm.^7,8 Lymph nodes >5 mm have a 50% to 70% chance of being malignant, while those <4 mm have only a 20% chance.^9,10 A new modality of endorectal ultrasound represents a three-dimensional (3-D) ERUS that provides better visual images of the tumor volume and spatial relations to the adjacent organs and structures, even better than those of MRI, which leads to better diagnostic accuracy than MRI and standard ERUS.^11–15 The unique 3-D–ERUS longitudinal scan can precisely assess the tumor size and location.¹⁶ The most important feature of this upgraded modality is the ability to reduce interpreter errors and offer potential predictive value. Three-dimensional ERUS provides the possibility to distinguish blood vessels from lymph nodes and allow precise fine needle aspiration (FNA) biopsies.^13,17 The infiltration of circumferential margin has been proven to correlate with T category, lymph node metastasis histologic tumor differentiation, and lymphovascular invasion.^13,17 Three-dimensional ERUS gives the possibility of multiplane evaluation of the tumor, allowing visualization of more subtle changes in the tumor characteristics and therefore better T and N categorizing.¹⁸ A review of 86 patients who underwent standard 3-D ERUS, ERUS and 4-channel detector computed tomography (CT) demonstrated T-category accuracy of 78%, 69%, and 57%, respectively.¹⁹ After analysis of the examiner''s error, the accuracy of 3-D ERUS for T category has reached 91% for 3-D ERUS and 88% for standard ERUS, and the N category accuracy improved to 90% and 76%, respectively. Also, ERUS can be used for diagnosis of premalignant lesions such as adenomas and polyps.²⁰ The main goal is to properly identify any chance of tumor invasion in the primary lesion and involvement of the surrounding lymph nodes in case the absence of those alarming characteristics allows for endoscopic resection of the lesion. Using higher-resolution probes, ERUS can distinguish T0 from T1 lesions. According to a meta-analysis of 258 biopsy-negative tumors, ERUS identified tumor mass in 81% of the 24 lesions, which were found to be invasive tumors on morphologic examination.²⁰ Another series of 60 patients with pT0/pT1 lesions demonstrated sensitivity and specificity of ERUS 89% and 88%, respectively.²¹ As with MRI, 3-D ERUS could provide an evaluation of the mesorectal fascia.^14,22The reported data lead to the position that 3-D ERUS combines the high-resolution images of the rectal wall and cost-effectiveness of standard ERUS with the multiplanar and stereoscopic imaging capabilities of MRI. Three-dimensional ERUS may be the future premier imaging modality used in rectal cancer management.     

Low-grade dietary-related inflammation and survival after colorectal cancer surgery

Purpose

Prolong inflammation is a central process observed in several chronic conditions and may be responsible for survival. There is an increasing evidence showing the role of diet in inflammation and habitual diet may be responsible for low-grade inflammation. The purpose of our study was to assess the effect of inflammatory properties of habitual diet measured by the Dietary Inflammatory Index (DII) on survival among surgical patients treated for colorectal cancer (CRC).

Methods

A follow-up study among 689 CRC patients (mean age 58 years, ±8.9; 56.7 % males) treated surgically was performed in Krakow, Poland. Habitual diet was assessed by a standardized semiquantitative food frequency questionnaire. Next, 23 dietary items were used to calculate DIIs. Vital records were verified to determine status of the participants.

Results

Study has shown linear association between DII and survival time among CRC patients with totally removed cancer treated by chemotherapy (b = ?0.13, p = 0.024). After adjustment for several important covariates, DII was associated with survival during up to 3 years after surgery, but only in patients without distant metastases (3-year HR_DII>?2.27 = 0.61, 95 % CI 0.38–0.99).

Conclusions

The results of the investigation have shown the usefulness of the DII as a potential predictor of survival among patients without distant metastases treated surgically for CRC.     

Pre-treatment of mice with tumor-conditioned media accelerates metastasis to lymph nodes and lungs: a new spontaneous breast cancer metastasis model

Current spontaneous metastasis models require a long period of observation after establishment of primary tumors to see significant metastatic progression. The degree of metastasis is not consistent among animals: this is problematic since it requires the use of a large number of animals to obtain reliable statistics. Here we report that pre-treatment of animals with tumor-conditioned media (TCM) consistently accelerates spontaneous metastasis in breast cancer. An inguinal breast tumor model facilitated by TCM showed robust anterior metastasis to the axillary and brachial lymph nodes (LN), and the lungs compared to the serum-free media treated group. The LN in TCM-treated animals showed enhanced angiogenesis and lymphangiogenesis. Primary tumors and lungs in TCM-treated animals showed enhanced lymphangiogenesis with no significant change in angiogenesis. TCM-treated animals also showed metastatic dissemination to abdomen from the primary injection site: this would generally enhance metastasis to other organs. In sum, the addition of TCM pre-treatment to current metastasis models results in accelerated and robust metastasis which would enable more efficient evaluation of anti-metastatic agents.