Person: Mullen, John
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Mullen
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Mullen, John
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Publication D2 Lymphadenectomy with Surgical Ex Vivo Dissection into Node Stations for Gastric Adenocarcinoma Can Be Performed Safely in Western Patients and Ensures Optimal Staging(Springer Nature, 2013) Schmidt, Benjamin; Chang, Kevin; Maduekwe, Ugwuji N.; Look-Hong, Nicole; Rattner, David; Lauwers, Gregory Y.; Mullen, John; Yang, Han-Kwang; Yoon, SamBACKGROUND: The AJCC recommends examination of >16 nodes to stage gastric adenocarcinoma. D2 lymphadenectomy (LAD) followed by surgical ex vivo dissection (SEVD) into nodal stations is standard at many high-volume Asian centers, but potential increases in morbidity and mortality have slowed adoption of D2 LAD in some Western centers. METHODS: A total of 331 patients with gastric adenocarcinoma who underwent surgical resection at one Western institution from 1995 to 2010 were examined. RESULTS: Median age of patients was 69 years old, 65% were male, and 84% were white. D1 LAD was performed in 285 patients (86%) and D2 LAD in 46 patients (14%), with SEVD being performed in 17 patients (37%) in the D2 group. D2 LAD with or without SEVD was performed much more commonly between 2006 and 2010. For the D1, D2 without SEVD, and D2 with SEVD groups, the median number of examined nodes and percentage with >16 examined nodes were 16 and 51%, 27 and 93%, and 40 and 100%, respectively. Major complications occurred in 16% of the D1 group and 17% of the D2 group (p>0.05), and 30-day mortality was 3% for the D1 group and 0% for the D2 group. D2 LAD was a positive prognostic factor for overall survival on univariate (p=0.027) and multivariate analyses (p=0.005), but there were several possible confounding variables. CONCLUSIONS: D2 LAD at our Western institution was performed with low morbidity and no mortality. Optimal staging occurred after D2 LAD combined with SEVD, where a median of 40 nodes were examined and all patients had >16 examined nodes.Publication Noncurative Gastrectomy for Gastric Adenocarcinoma Should only be Performed in Highly Selected Patients(Springer Nature, 2013) Schmidt, Benjamin; Look-Hong, Nicole; Maduekwe, Ugwuji N.; Chang, Kevin; Hong, Theodore; Kwak, Eunice Lee; Lauwers, Gregory Y.; Rattner, David; Mullen, John; Yoon, SamBackground: The benefit of surgical resection in patients with incurable gastric adenocarcinoma is controversial. Methods: A total of 289 patients who presented with advanced or metastatic gastric cancer from 1995 to 2010 were retrospectively reviewed. Results: Ten patients (3.5 %) required emergent surgery at presentation and were excluded from further analyses. Patients who underwent nonemergent surgery at presentation (n = 110, 38.1 %) received either gastric resection (group A, n = 46, 42 %) or surgery without resection (group B, n = 64, 58 %). Procedures in group A included distal gastrectomy (n = 25, 54 %), total gastrectomy (n = 17, 37 %), and proximal/esophagogastrectomy (n = 4, 9 %). Procedures in group B included laparoscopy (n = 17, 27 %), open exploration (n = 25, 39 %), gastrostomy and/or jejunostomy tube (n = 12, 19 %), and gastrojejunostomy (n = 10, 16 %). Group A required a stay in the intensive care unit or additional invasive procedure significantly more often than group B (15 vs. 2 %, p = 0.009). Four patients in group A (8.7 %) and three patients in group B (4.7 %) died within 30 days of surgery (p = 0.45). When the 110 patients who underwent nonemergent surgery (groups A and B) were compared to nonoperatively managed patients (group C, n = 169, 58 %), median overall survival did not significantly differ (8.6 vs. 9.2 vs. 7.7 months; p > 0.05). Three patients in group B (4.7 %) and three in group C (1.8 %) ultimately required an operation for their primary tumor. Conclusions: Patients with gastric adenocarcinoma who present with advanced or metastatic disease not amenable to curative resection infrequently require emergent surgery. Noncurative resection is associated with significant perioperative morbidity and mortality as well as limited overall survival, and should therefore be performed judiciously.Publication Vitamin D Status and the Risk of Anemia in Community-Dwelling Adults: Results from the National Health and Nutrition Examination Survey 2001–2006(Wolters Kluwer Health, 2015) Monlezun, Dominique J.; Camargo, Carlos; Mullen, John; Quraishi, SadeqAbstract Low vitamin D status has been implicated in several chronic medical conditions and unfavorable health outcomes. Our goal was to investigate whether serum 25-hydroxyvitamin D (25OHD) levels are a potentially modifiable risk factor for anemia in a nationally representative cohort of community-dwelling individuals in the United States. We performed a cross-sectional study of 5456 individuals (≥17 years) from the National Health and Nutrition Examination Survey from 2001 to 2006. Locally weighted scatterplot smoothing (LOWESS) was used to graphically depict the relationship between serum 25OHD levels and the cumulative frequency of anemia. Multivariable logistic regression models were then used to assess the independent association of 25OHD levels with anemia, while controlling for age, sex, race, body mass index, chronic kidney disease, as well as serum levels of C-reactive protein, ferritin, iron, vitamin B12, and folic acid. The mean (standard error) 25OHD and hemoglobin levels in the analytic group were 23.5 (0.4) ng/mL and 14.4 (0.1) g/dL, respectively. Prevalence of anemia was 3.9%. Locally weighted scatterplot smoothing analysis demonstrated a near-linear relationship between vitamin D status and cumulative frequency of anemia up to 25OHD levels of approximately 20 ng/mL. With increasing 25OHD levels, the curve flattened out progressively. Multivariable regression analysis demonstrated an inverse association of 25OHD levels with the risk of anemia (adjusted odds ratio 0.97; 95% confidence interval 0.95–0.99 per 1 ng/mL change in 25OHD). Compared to individuals with ≥20 ng/mL, individuals with 25OHD levels <20 ng/mL were more likely to be anemic (adjusted odds ratio 1.64; 95% confidence interval 1.08–2.49). In a nationally representative sample of community-dwelling individuals in the United States, low 25OHD levels were associated with increased risk of anemia. Randomized controlled trials are needed to determine whether optimizing vitamin D status can reduce the burden of anemia in the general population.Publication Primary Kaposi Sarcoma of the Subcutaneous Tissue(BioMed Central, 2008) Pantanowitz, Liron; Mullen, John; Dezube, Bruce JBackground: Involvement of the subcutis by Kaposi sarcoma (KS) occurs primarily when cutaneous KS lesions evolve into deep penetrating nodular tumors. Primary KS of the subcutaneous tissue is an exceptional manifestation of this low-grade vascular neoplasm. Case presentation: We present a unique case of acquired immune deficiency syndrome (AIDS)-associated KS manifesting primarily in the subcutaneous tissue of the anterior thigh in a 43-year-old male, which occurred without overlying visible skin changes or concomitant KS disease elsewhere. Radiological imaging and tissue biopsy confirmed the diagnosis of KS. Conclusion: This is the first documented case of primary subcutaneous KS occurring in the setting of AIDS. The differential diagnosis of an isolated subcutaneous lesion in an human immunodeficiency virus (HIV)-infected individual is broad, and requires both imaging and a histopathological diagnosis to guide appropriate therapy.Publication Opposing Immune and Genetic Mechanisms Shape Oncogenic Programs in Synovial Sarcoma(Cold Spring Harbor Laboratory, 2021-01-25) Jerby-Arnon, Livnat; Neftel, Cyril; Shore, Marni E.; Weisman, Hannah R.; Mathewson, Nathan; McBride, Matthew J.; Haas, Brian; Izar, Benjamin; Volorio, Angela; Boulay, Gaylor; Cironi, Luisa; Richman, Alyssa R.; Broye, Liliane C.; Gurski, Joseph M.; Luo, Christina; Mylvaganam, Ravindra; Nguyen, Lan; Mei, Shaolin; Melms, Johannes; Georgescu, Christophe; Cohen, Ofir; Buendia Buendia, Jorge Eduardo; Segerstolpe, Asa; Sud, Malika; Cuoco, Michael; Labes, Danny; Zollinger, Daniel R.; Ortogero, Nicole; Beechem, Joseph M.; Nielsen, G. Petur; Chebib, Ivan; Nguyen-Ngoc, Tu; Montemurro, Michael; Cote, Gregory; Choy, Edwin; Letovanec, Igor; Cherix, Stéphane; Wagle, Nikhil; Sorger, Peter; Haynes, Alex; Mullen, John; Stamenkovic, Ivan; Rivera, Miguel; Kadoch, Cigall; Wucherpfennig, Kai; Rozenblatt-Rosen, Orit; Suvà, Mario L.; Riggi, Nicolò; Regev, AvivABSTRACTSynovial sarcoma is an aggressive mesenchymal neoplasm, driven by the SS18-SSX fusion, and characterized by immunogenic antigens expression and exceptionally low T cell infiltration levels. To study the cancer-immune interplay in this disease, we profiled 16,872 cells from 12 human synovial sarcoma tumors using single-cell RNA-sequencing (scRNA-Seq). Synovial sarcoma manifests antitumor immunity, high cellular plasticity and a core oncogenic program, which is predictive of low immune levels and poor clinical outcomes. Using genetic and pharmacological perturbations, we demonstrate that the program is controlled by the SS18-SSX driver and repressed by cytokines secreted by macrophages and T cells in the tumor microenvironment. Network modeling predicted that SS18-SSX promotes the program through HDAC1 and CDK6. Indeed, the combination of HDAC and CDK4/6 inhibitors represses the program, induces immunogenic cell states, and selectively targets synovial sarcoma cells. Our study demonstrates that immune evasion, cellular plasticity, and cell cycle are co-regulated and can be co-targeted in synovial sarcoma and potentially in other malignancies.