Current and novel mapping substances in gynecologic cancer care.

Many tracers have been introduced into current medical practice with the purpose of improving lymphatic mapping techniques, anatomic visualization, and organ/tissue perfusion assessment. Among them, three tracers have dominated the field: indocyanine green, technetium-99m radiocolloid (Tc99m), and blue dye. Tc99m and blue dye are used individually or in combination; however, given particular challenges with these tracers, such as the need for a preoperative procedure by nuclear medicine and cost, other options have been sought. Indocyanine green has proven to be a promising alternative for certain procedures, as it is easy to use and has quick uptake. Its use in the management of gynecologic cancers was first described for sentinel lymph node mapping in cervical cancer, and later for endometrial and vulvar cancers. This review provides an in-depth look at these mapping substances, their uses, and the potential for new discoveries.

Immunotherapy for ovarian cancer is improved by tumor targeted delivery of a neoantigen surrogate.

Ovarian cancer is known for its poor neoantigen expression and strong immunosuppression. Here, we utilized an attenuated non-pathogenic bacterium Listeria monocytogenes to deliver a highly immunogenic Tetanus Toxoid protein (Listeria-TT), as a neoantigen surrogate, into tumor cells through infection in a metastatic mouse ovarian cancer model (Id8p53-/-Luc). Gemcitabine (GEM) was added to reduce immune suppression. Listeria-TT+GEM treatments resulted in tumors expressing TT and reactivation of pre-existing CD4 and CD8 memory T cells to TT (generated early in life). These T cells were then attracted to the TT-expressing tumors now producing perforin and granzyme B. This correlated with a strong reduction in the ovarian tumors and metastases, and a significant improvement of the survival time compared to all control groups. Moreover, two treatment cycles with Listeria-TT+GEM doubled the survival time compared to untreated mice. Checkpoint inhibitors have little effect on ovarian cancer partly because of low neoantigen expression. Here we demonstrated that Listeria-TT+GEM+PD1 was significantly more effective (efficacy and survival) than PD1 or Listeria-TT+GEM alone, and that more treatment cycles with Listeria-TT+GEM+PD1 significantly increased the survival time compared to Listeria-TT+GEM alone. In summary, the results of this study suggest that our approach may benefit ovarian cancer patients.

Body composition in amyotrophic lateral sclerosis subjects and its effect on disease progression and survival.

BACKGROUND: Motor neuron degeneration and malnutrition alter body composition in amyotrophic lateral sclerosis (ALS). Resulting losses of weight, fat mass (FM), and fat-free mass (FFM) shorten survival. Nutritional management relies on body weight or BMI; neither reliably indicates malnutrition nor differentiates body compartments. OBJECTIVES: We aimed to 1) develop an equation to compute FM and FFM using clinical data, validated against DXA; and 2) examine the effect of computed FM and FFM on disease course and survival. METHODS: We studied 364 ALS patients from 3 cohorts. In Cohort #1 we used logistic regression on clinical and demographic data to create an equation (test cohort). In Cohort #2 we validated FM and FFM computed using this equation against DXA (validation cohort). In Cohort #3, we examined the effect of computed body composition on disease course and survival. RESULTS: In Cohort #1 (n = 29) the model incorporated sex, age, BMI, and bulbar-onset to create an equation to estimate body fat: % body fat = 1.73 - [19.80*gender (1 if male or 0 if female)] + [0.25*weight (kg)] + [0.95*BMI (kg/m2)] - (5.20*1 if bulbar-onset or *0 if limb-onset). In Cohort #2 (n = 104), body composition using this equation, compared to other published equations, showed the least variance from DXA values. In Cohort #3 (n = 314), loss of body composition over 6 mo was greater in males. Adjusted survival was predicted by low baseline FM (HR: 1.39; 95% CI: 1.07, 1.80), and loss of FM (HR: 1.87; 95% CI: 1.30, 2.69) and FFM (HR: 1.73; 95% CI: 1.20, 2.49) over 6 mo. CONCLUSIONS: Our equation broadens the traditional nutritional evaluation in clinics and reliably estimates body composition. Measuring body composition could target FM as a focus for nutritional management to ensure adequate energy intake and complement measures, such as the ALS functional rating scale-revised score and forced vital capacity, currently used.