The past, present, and future of immunotherapy for colorectal cancer.

Colorectal cancer is prevalent worldwide, with various factors influencing the survival rate of late-stage metastatic cases. Current standard treatments include surgical removal, adjuvant chemotherapy, and neoadjuvant chemotherapy. Novel immunotherapy research shows promising results for various cancer types, including colorectal cancer. Current immunotherapy options are limited to specific molecular subtypes of colorectal cancer, while the remaining are limited to standard protocol. This review article summarizes approved, developing, and potential sources for novel colorectal cancer immunotherapy treatment through active-specific, checkpoint inhibitor, cytokine, cytotoxic, and adoptive T-cell immunotherapy. Such a study would be beneficial to patients with colorectal cancer.

Image Distortion During Flexible Ureteroscopy: A Laboratory Model Comparing Super Pulsed Thulium Fiber Laser vs High-Power Ho:YAG Laser.

Purpose: Digital ureteroscopes employ "chip-on-the-tip" technology that allows for significant improvement in image resolution. However, image distortion often occurs during laser lithotripsy owing to acoustic wave production. We sought to compare image distortion using different laser power settings and distances from the laser fiber tip to the scope for the Super Pulsed Thulium Fiber (SPTF) laser and high-power Holmium:YAG (Ho:YAG) laser. Materials and Methods: Ureteroscopy was simulated using a silicon kidney-ureter-bladder model fitted with a 12F/14F access sheath and the Lithovue™ (Boston Scientific), disposable digital flexible ureteroscope. At defined laser parameters (10, 20, 30 and 40 W, short pulse), a 200-µm laser fiber was slowly retracted toward the tip of the ureteroscope during laser activation. Image distortion was identified, and distance from the laser tip to the scope tip was determined. Data from the two lasers were compared utilizing t-tests. Results: After controlling for frequency, power, and laser mode, utilizing 1.0 J of energy was significantly associated with less feedback than 0.5 J (-0.091 mm, p ≤ 0.05). Increased power was associated with larger feedback distance (0.016 mm, p ≤ 0.05); however, increase in frequency did not have a significant effect (-0.001 mm, p = 0.39). The SPFT laser had significantly less feedback when compared with all Holmium laser modes. Conclusions: Increased total power results in image distortion occurring at greater distances from the tip of the ureteroscope during laser activation. Image distortion occurs further from the ureteroscope with Ho:YAG laser than with SPTF fibers at the same laser settings. In clinical practice, the tip of the laser fiber should be kept further away from the tip of the scope during ureteroscopy as the power increases as well as when utilizing the Ho:YAG system compared with the SPTF laser platform. The SPTF laser may have a better safety profile in terms of potential scope damage.

Genomic and Functional Variation of the Chlorophyll d-Producing Cyanobacterium Acaryochloris marina.

The Chlorophyll d-producing cyanobacterium Acaryochloris marina is widely distributed in marine environments enriched in far-red light, but our understanding of its genomic and functional diversity is limited. Here, we take an integrative approach to investigate A. marina diversity for 37 strains, which includes twelve newly isolated strains from previously unsampled locations in Europe and the Pacific Northwest of North America. A genome-wide phylogeny revealed both that closely related A. marina have migrated within geographic regions and that distantly related A. marina lineages can co-occur. The distribution of traits mapped onto the phylogeny provided evidence of a dynamic evolutionary history of gene gain and loss during A. marina diversification. Ancestral genes that were differentially retained or lost by strains include plasmid-encoded sodium-transporting ATPase and bidirectional NiFe-hydrogenase genes that may be involved in salt tolerance and redox balance under fermentative conditions, respectively. The acquisition of genes by horizontal transfer has also played an important role in the evolution of new functions, such as nitrogen fixation. Together, our results resolve examples in which genome content and ecotypic variation for nutrient metabolism and environmental tolerance have diversified during the evolutionary history of this unusual photosynthetic bacterium.

Multiresolution Modeling of High-Latitude Ionospheric Electric Field Variability and Impact on Joule Heating Using SuperDARN Data.

The most dynamic electromagnetic coupling between the magnetosphere and ionosphere occurs in the polar upper atmosphere. It is critical to quantify the electromagnetic energy and momentum input associated with this coupling as its impacts on the ionosphere and thermosphere system are global and major, often leading to considerable disturbances in near-Earth space environments. The current general circulation models of the upper atmosphere exhibit systematic biases that can be attributed to an inadequate representation of the Joule heating rate resulting from unaccounted stochastic fluctuations of electric fields associated with the magnetosphere-ionosphere coupling. These biases exist regardless of geomagnetic activity levels. To overcome this limitation, a new multiresolution random field modeling approach is developed, and the efficacy of the approach is demonstrated using Super Dual Auroral Radar Network (SuperDARN) data carefully curated for the study during a largely quiet 4-hour period on February 29, 2012. Regional small-scale electrostatic fields sampled at different resolutions from a probabilistic distribution of electric field variability conditioned on actual SuperDARN LOS observations exhibit considerably more localized fine-scale features in comparison to global large-scale fields modeled using the SuperDARN Assimilative Mapping procedure. The overall hemispherically integrated Joule heating rate is increased by a factor of about 1.5 due to the effect of random regional small-scale electric fields, which is close to the lower end of arbitrarily adjusted Joule heating multiplicative factor of 1.5 and 2.5 typically used in upper atmosphere general circulation models. The study represents an important step toward a data-driven ensemble modeling of magnetosphere-ionosphere-atmosphere coupling processes.

Adrenal-Renal Fusion with Adrenal Cortical Adenoma and Ectopic Adrenal Tissue, Presenting as Suspected Renal Mass: A Case Report.

Adrenal-renal fusion with adrenal cortical adenoma is a rare anomaly with only a few cases described in the literature. Imaging-based identification of this anomaly remains a diagnostic challenge, making it difficult to differentiate upper pole renal malignancy from adrenal cortical adenoma. We describe a case of a 62-year-old woman with an upper pole cystic renal mass on imaging, who underwent robotic partial nephrectomy. Intraoperatively the renal mass was found to be an adrenal-renal fusion anomaly, with ectopic adrenal tissue. Adrenal-renal infusion of an adrenal cortical adenoma was confirmed on final pathology. Due to lack of imaging-based diagnosis, this condition should be considered in the differential for upper pole renal masses.

Enterocystoplasty and appendicovesicostomy in adults: a description of demographics and 30-day outcomes of bladder augmentation.

Within the adult population, studies of the granular clinical outcomes of appendicovesicostomy (AV) and augmentation enterocystoplasty (AE) have been limited to case series. Using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data, this study sought to describe the population undergoing these procedures. An analysis of the ACS NSQIP database (2015 to 2018) was performed, capturing patients with procedure codes of enterocystoplasty with intestinal anastomosis or cutaneous appendicovesicostomy. Patients were stratified into three groups, if they underwent either procedure, or both procedures. Demographics, comorbidities, perioperative variables, surgeon specialty, and outcomes were described. 130 patients undergoing AV or AE were captured. Most of these patients were white (70.77%) and middle aged (46.78±17.33 years). Most patients were an American Society of Anesthesiologists class 3 or greater risk (71.54%). A higher percentage of AE patients were readmitted, returned to the operating room, and had postoperative UTI or sepsis compared to those undergoing AV or AV+AE. The most common complication overall was readmission related to the operation (14.62%). The most common postoperative diagnosis was neurogenic related in over half of cases. The study shows patients undergoing bladder augmentation and appendicovesicostomy are readmitted not infrequently. Risk of infection, sepsis, bleeding, and reoperation are also not insignificant. Further studies should be carried out to aid in decreasing complication rate and readmissions after these procedures.

Lymph node density for stratification of survival outcomes with node positive upper tract urothelial carcinoma.

INTRODUCTION: The use of lymph node density (LND) as a predictor of survival outcomes has been studied with urothelial carcinoma of the bladder. Similar results can be postulated to upper tract urothelial carcinoma (UTUC). This study aims to determine the overall survival of patients with lymph node positive UTUC based on LND, utilizing the National Cancer Database (NCDB). MATERIALS AND METHODS: Data was derived from NCDB Participant User Kidney Dataset using the histology code 'transitional cell carcinoma', utilizing pN+ patients from 2004-2015. LND was calculated as number of positive nodes divided by total number of nodes removed. Patients were stratified by traditional AJCC pN stage and compared to LND groups (< 30%, ≥ 30%). Primary outcome was overall survival. Kaplan-Meier and Cox regression analyses were performed. RESULTS: A total of 2049 patients were identified (pN1 = 1022, pN2 = 1027; LND < 30% = 370, ≥ 30% = 1679). Mean LND was 71%. Cox regression for mortality using pN stage was not significant (p = 0.11); however, Cox regression for mortality using LND group noted significantly worsened survival with LND ≥ 30% (HR 1.54, p = 0.001). Kaplan Meier analysis for overall survival at 2 years showed no difference between pN1 and pN2 stages (35.3% versus 34.1%; log rank p = 0.37). Kaplan Meier analysis for overall survival at 2 years revealed significant difference between LND groups (LND < 30%, 47.3% versus LND ≥ 30%, 32.0%; log rank p < 0.001). CONCLUSIONS: LND provides improved prognostic information regarding overall survival, compared to traditional AJCC pN staging. Future studies need to evaluate LND to improve prognostic understanding of lymph node positive UTUC.

Trends in the treatment of clinical T1 renal cell carcinoma for octogenarians: Analysis of the National Cancer Database.

OBJECTIVE: Treatment of renal cell carcinoma has evolved with emphasis on nephron preservation for small renal masses. Our objective was to evaluate the proportions of treatment types for octogenarians with clinical stage 1 renal cell carcinoma. MATERIALS AND METHODS: The National Cancer Database was analyzed from 2004 to 2015. Patients with clinical stage 1, tumor size ≤ 7 cm, and age 80-89 years old were compared to a younger control arm of patients ≤ 70 years old. Treatment modality was categorized as radical nephrectomy (RN), partial nephrectomy (PN), percutaneous ablative therapy (PAT), and no treatment (NT). Primary outcome was treatment utilization over time using estimated annual percentage change (EAPC). Secondary outcomes included logistic regression for 30 day readmission after treatment and any definitive tumor treatment choice. RESULTS: 18,903 octogenarians were identified and compared to a control of 142,179 patients ≤ 70 years old. Overall, NT (36%) was the most common modality for octogenarians while PN (44.8%) was most common for the control arm. Using EAPC for octogenarians, we found increases for PAT (7.1%), PN (2.8%), and NT (1.6%) but a decrease for RN (-4.6%). EAPC for the younger cohort noted increases for PAT (6.8%), PN (5.4%), and NT (4.4%) but a decrease for RN (-5.5%). CONCLUSION: For octogenarians with stage 1 renal cell carcinoma, minimally invasive treatments are increasingly utilized, while RN is decreasing. Compared to a younger cohort, a greater proportion of octogenarians are receiving NT. These findings remain encouraging for appropriate treatment of localized disease in patients with advanced age.