Lymphatics, Volume 2, Issue 2 (June 2024) – 5 articles

Complex atypical endometrial hyperplasia (CAH) carries a high probability of cancer. The intraoperative evaluation of endometrial cancer in cases of CAH has not been reliable. The safety and sensitivity of sentinel lymph node (SLN) sampling has been validated. In our study, we aimed to evaluate the efficacy and safety of SLN sampling in CAH managed by the da Vinci robotic platform. A total of 113 patients with a preoperative diagnosis of CAH were included in this retrospective cohort study. All of them underwent a robot-assisted total laparoscopic hysterectomy and bilateral salpingo-oophorectomy, with 69 patients undergoing SLN sampling. A statistical analysis calculated the probability of cancer, the SLN map rate, and surgical complications. The predictors of cancer were evaluated. Descriptive statistics were used to summarize the results; comparative statistics were used to compare the cohorts; and logistical regression analysis was used to predict the risk. Forty-seven percent of the entire cohort was diagnosed with endometrial cancer. The median age was 63 years in the SLN cohort (N = 69) and 61 in the No-SLN cohort (N = 44) (p = 0.363). The median BMI was 34 Kg/m² in the SLN cohort and 40 in the No-SLN cohort (p = 0.004). The bilateral SLN map was 92.8%, and the unilateral SLN map rate was 7.2%. There were no grade-3–4 complications in the SLN cohort, and four grade-3–4 complications in the No-SLN group (p = 0.021). A preoperative diagnosis of CAH bordering on or unable to rule out cancer was the only predictor of cancer. Sentinel lymph node sampling has a high map rate and low complications in CAH. We recommend a prospective study investigating the clinical benefit of the procedure. Full article

The studies of thymic structure were performed predominantly in cohorts of younger individuals. Here, we established a cohort of body donors whose age at the time of death ranged from 57 to 103 to study the relationship between thymic structure and factors that, in the younger subjects, have shown to affect the organ’s anatomy, including the presence of the organ’s capsule, its weight, size of the left and right lobes, and a transverse diameter. We explored the relationships between these thymic parameters and the subjects’ age, sex, and cause of death (COD), asking how the thymus in the elderly differed from the organ’s macro-anatomy in a broader and younger human population, and whether age, sex, COD, and BMI could influence the thymic parameters in the elderly. Our analyses revealed that the thymic size but not thymic weight in the KYCOM cohort differed significantly from the younger individuals. The size of the thymus in males progressively decreased, but in females, the size of the right lobe increased. The encapsulated thymus was detected with a higher frequency in females than males. We found no associations between thymic parameters and the person’s COD, age, or sex. However, the person’s BMI was associated with thymic weight, suggesting that obesity may influence the aging of the immune system. Full article

CLL B cells express elevated pro-survival BCL2, and its selective inhibitor, venetoclax, significantly reduces leukemic cell load, leading to clinical remission. Nonetheless, relapses occur. This study evaluates the hypothesis that progressively diminished BCL2 protein in cycling CLL cells within patient lymph node niches contributes to relapse. Using CFSE-labeled, purified CLL populations known to respond with vigorous cycling in d6 cultures stimulated with TLR9-activating ODN (oligodeoxynucleotide) + IL15, we show that BCL2 protein progressively declines during consecutive cell divisions. In contrast, MCL1 and survivin are maintained/slightly elevated during cycling. Delayed pulsing of quiescent and activated CLL cultures with selective inhibitors of BCL2 or survivin revealed selective targeting of noncycling and cycling populations, respectively, raising implications for therapy. To address the hypothesis that BCL2-repressive miRs (miR15a/miR16-1), encoded in Chr13, are mechanistically involved, we compared BCL2 protein levels within ODN + IL15-stimulated CLL cells, with/without del(13q), yielding results suggesting these miRs contribute to BCL2 reduction. In support, within ODN-primed CLL cells, an IL15-driven STAT5/PI-3K pathway (required for vigorous cycling) triggers elevated p53 TF protein known to directly activate the miR15a/miR16-1 locus. Furthermore, IL15 signaling elicits the repression of BCL2 mRNA within 24 h. Additional comparisons of del(13q)+ and del(13q)−/− cohorts for elevated p53 TF expression during cycling suggest that a documented miR15a/miR16-1-mediated negative feedback loop for p53 synthesis is active during cycling. Findings that robust CLL cycling associates with progressively decreasing BCL2 protein that directly correlates with decreasing venetoclax susceptibility, combined with past findings that these cycling cells have the greatest potential for activation-induced cytosine deaminase (AICDA)-driven mutations, suggest that venetoclax treatment should be accompanied by modalities that selectively target the cycling compartment without eliciting further mutations. The employment of survivin inhibitors might be such an approach. Full article

The foot and calf muscle pump, collectively known as the venous muscle pump, plays a crucial role in the circulatory system (veins, arteries, and lymphatics), particularly in the return of blood from the lower extremities to the heart. Further, the venous muscle pump is crucial to lymphatic health and essential in chronic edema/lymphedema management. This article will highlight the significance of the venous pump and review the functional anatomy and physiology of the foot and calf, integrating the connection to venous and lymphatic health. The complementary importance of mobility, exercise, and breathing will also be explored. Full article