Lymphadenopathy in Fungating Extremity Soft-Tissue Sarcoma: Metastasis or Reactive?

BACKGROUND: Patients with fungating extremity soft-tissue sarcoma (STS) can develop lymphadenopathy, which can represent nodal metastasis or benign reactive adenopathy. METHODS: In 1787 patients with STS, 67 (3.7%) had fungating extremity STS. In the 62 patients who met our inclusion criteria, we evaluated prevalence and histopathology of lymphadenopathy, factors associated with lymphadenopathy and nodal metastasis, and prevalence of and factors associated with lung metastasis and survival time from fungation. Logistic regression and Cox proportional-hazards models were used to analyze node pathology, lung metastasis, and survival duration with α = 0.05. RESULTS: Lymphadenopathy occurred in 11 of 62 patients (18%), 6 with nodal metastasis and 5 with reactive adenopathy. The only factor associated with lymphadenopathy was location of primary tumor in the upper extremity (p = 0.02). No tumor characteristics were associated with nodal metastasis. In all five patients with reactive adenopathy, the condition was recognized within 3 days after tumor fungation. Lymphadenopathy recognized more than 3 days after tumor fungation was likely to be nodal metastasis. Forty-one percent of patients developed lung metastasis, which was not associated with presence of lymphadenopathy or any patient or tumor characteristic. Age, tumor size, and Black and Asian race were independently associated with greater risk of death. CONCLUSIONS: Eighteen percent of patients with fungating extremity STS developed lymphadenopathy. Approximately half of cases represented nodal metastasis, and half represented reactive adenopathy. Lymphadenopathy that develops within 3 days after tumor fungation should increase suspicion for reactive adenopathy versus nodal metastasis.

Tumorigenicity of hypoxic respiring cancer cells revealed by a hypoxia-cell cycle dual reporter.

Although aerobic glycolysis provides an advantage in the hypoxic tumor microenvironment, some cancer cells can also respire via oxidative phosphorylation. These respiring ("non-Warburg") cells were previously thought not to play a key role in tumorigenesis and thus fell from favor in the literature. We sought to determine whether subpopulations of hypoxic cancer cells have different metabolic phenotypes and gene-expression profiles that could influence tumorigenicity and therapeutic response, and we therefore developed a dual fluorescent protein reporter, HypoxCR, that detects hypoxic [hypoxia-inducible factor (HIF) active] and/or cycling cells. Using HEK293T cells as a model, we identified four distinct hypoxic cell populations by flow cytometry. The non-HIF/noncycling cell population expressed a unique set of genes involved in mitochondrial function. Relative to the other subpopulations, these hypoxic "non-Warburg" cells had highest oxygen consumption rates and mitochondrial capacity consistent with increased mitochondrial respiration. We found that these respiring cells were unexpectedly tumorigenic, suggesting that continued respiration under limiting oxygen conditions may be required for tumorigenicity.

Postoperative Opioid Use Following Single-Level Transforaminal Lumbar Interbody Fusion Compared with Posterolateral Lumbar Fusion.

OBJECTIVE: To compare postoperative opioid morphine milligram equivalents (MME) prescriptions for opioid-naïve patients undergoing single-level transforaminal lumbar interbody fusion (TLIF) versus posterolateral lumbar fusion (PLF) and total postoperative MME prescribed based on operative duration. METHODS: Patients undergoing single-level TLIF or PLF from September 2017 to June 2020 were identified from a single institution. Patients were first grouped based on procedure type (TLIF or PLF) and subsequently regrouped based on median operative duration. Statistical tests compared patient demographics and opioid prescription data between groups. Multivariate regressions were performed to control for demographics, operative time, and procedure type. RESULTS: Of 345 patients undergoing single-level PLF or TLIF, 174 (50.4%) were opioid-naïve; 101 opioid-naïve patients (58.0%) underwent PLF and 73 (42.0%) underwent TLIF. Patients undergoing TLIF received more opioid prescriptions (1.99 vs. 1.26, P < 0.001) and total MME (91.2 vs. 66.8, P = 0.002). After regrouping patients based on operative duration, independent of procedure type, there were no differences in postoperative opioid prescriptions, and Spearman rank correlation coefficient between total MME and operative duration was r = 0.014. Multivariate analysis identified TLIF as an independent predictor of increased postoperative opioid prescriptions (ß = 0.64, P < 0.001), prescribers (ß = 0.49, P = 0.003), and MME (ß = 24.4, P = 0.030). CONCLUSIONS: Opioid-naïve patients undergoing single-level TLIF receive a greater number of postoperative opioids than patients undergoing single-level PLF, and TLIF was an independent predictor of increased postoperative opioid prescribers, prescribers, and MME. There were no differences in postoperative opioid prescriptions when assessing patients based on operative duration.