Background: The breast is a rare extranodal site of non-Hodgkin lymphoma, and primary breast lymphoma (PBL) has been arbitrarily defined as disease localized to one or both breasts with or without regional lymph nodes involvement. The aim of this study was to evaluate the clinical outcomes in patients with diffuse large B cell lymphoma (DLBCL) and breast involvement, and to find the criteria of PBL reflecting the outcome and prognosis. Methods: We retrospectively analyzed data from 68 patients, newly diagnosed with DLBCL and breast involvement at 16 Korean institutions between January 1994 and June 2009. Results: Median age at diagnosis was 48 years (range, 20-83 years). Forty-three (63.2%) patients were PBL according to previous arbitrary criteria, sixteen (23.5%) patients were high-intermediate to high risk of international prognostic index. The patients with one extranodal disease in the breast (OED) with or without nodal disease were 49 (72.1%), and those with multiple extranodal disease (MED) were 19 (27.9%). During median follow-up of 41.5 months (range, 2.4-186.0 months), estimated 5-year progression-free survival (PFS) was 53.7 ± 7.6%, and overall survival (OS) was 60.3 ± 7.2%. The 5-year PFS and OS was significantly higher for patients with the OED group than those with the MED group (5-year PFS, 64.9 ± 8.9% vs. 27.5 ± 11.4%, p = 0.001; 5-year OS, 74.3 ± 7.6% vs. 24.5 ± 13.0%, p < 0.001). In multivariate analysis, MED (hazard ratio [HR], 3.61; 95% confidence interval [CI], 1.07-12.2) and fewer than four cycles of systemic chemotherapy with or without local treatments (HR, 4.47; 95% CI, 1.54-12.96) were independent prognostic factors for worse OS. Twenty-five (36.8%) patients experienced progression, and the cumulative incidence of progression in multiple extranodal sites or other than breasts and central nervous system was significantly different between the OED group and the MED group (5-year cumulative incidence, 9.7 ± 5.4% vs. 49.0 ± 15.1%, p = 0.001). Conclusions: Our results show that the patients included in OED group, reflecting different treatment outcome, prognosis and pattern of progression, should be considered as PBL in the future trial. Further studies are warranted to validate our suggested criteria.

Bang SM, et al. J Korean Med Sci. 2014 Feb;29(2):164-171. https://doi.org/10.3346/jkms.2014.29.2.164

Limited data is available regarding the pharmacological prophylaxis for venous thromboembolism (VTE) in Asian patients undergoing total knee arthroplasty or total hip arthroplasty (TKA/THA). We performed a population-based epidemiological study using the Health Insurance Review and Assessment Service database to estimate the rate of pharmacological thromboprophylaxis and its impact on VTE in Korean patients who underwent TKA/THA between 2009 and 2013. We identified 306,912 cases (TKA, 261,260; THA, 45,652). The pharmacological thromboprophylaxis rate was 57.16% (TKA, 58.32%; THA, 50.51%), which increased from 42.81% in 2009 to 65.92% in 2013 (P = 0.0165). Both low-molecular-weight-heparin (22.42%) and rivaroxaban (22.71%) were the most common drugs for prophylaxis. The number of patients aged ≥ 60 years (87.31% vs. 81.01%, P < 0.0001), cases requiring general anesthesia (20.70% vs. 18.37%, P < 0.0001), and cases requiring long hospital stay (median, 13 days vs. 12 days, P < 0.0001) were significantly greater in the pharmacological prophylaxis group. The incidence of VTE within 3 months of surgery was 1.52% (TKA, 1.46%; THA, 1.87%). Patients with pharmacological prophylaxis had higher VTE rates (TKA, 1.69% vs. 1.14%; THA, 2.30% vs. 1.43%) than those without prophylaxis, with advanced age, use of general anesthesia, and a longer hospital stay increasing the risk of VTE. However, rivaroxaban significantly reduced the incidence of VTE following TKA (0.82% vs. 1.14%; odd ratio [OR], 0.72; 95% CI, 0.65–0.79). Moreover, ≥ 10 days of pharmacological thromboprophylaxis was significantly associated with lower incidence of VTE after TKA (1.33% vs. 1.52%; OR, 0.87; 95% CI, 0.81–0.94). This represents the largest epidemiological study showing a gradual increase in the use of pharmacological prophylaxis in Korean patients undergoing TKA/THA. Although the incidence of VTE is still low without pharmacological prophylaxis, this study demonstrates that the incidence of VTE can be reduced further using appropriate pharmacological thromboprophylaxis strategies.

Kook MH, et al. Korean J Intern Med. 2014 Jan;29(1):123-125. http://dx.doi.org/10.3904/kjim.2014.29.1.123

Nitric oxide (NO) synthesis is strongly induced during interleukin (IL)-2 treatment of mice and humans. Although this free radical can act as a cytotoxic effector molecule against cancer cells, immunosuppressive effects have also been suggested. We evaluated the effects of curcumin on IL-2-induced NO synthesis and IL-2-induced antitumor responses in a mouse ascites tumor model. Curcumin inhibited inducible nitric oxide synthase (iNOS) expression and NO production, and thereby enhanced the proliferation and cytotoxic activity of cocultured lymphocytes and macrophages during IL-2 stimulation which we earlier established as an in vitro model of IL-2-induced NO synthesis. Curcumin also decreased apoptosis of cocultured lymphocytes and macrophages during IL-2 stimulation. In contrast, the curcumin-induced changes in proliferation and apoptosis were not observed in cultures of lymphocytes alone, macrophages alone, and cocultured lymphocytes/iNOS-knock out macrophages, all of which produced little nitrite during IL-2 stimulation. In conjunction with IL-2 treatment, oral curcumin administration significantly inhibited IL-2 therapy-induced urinary nitrite/nitrate excretion and iNOS expression of tumor tissues, and further increased the IL-2 therapy-induced prolongation of survival in a murine Meth-A ascites tumor model. Curcumin may be useful as an adjunct to increase the antitumor activity of IL-2 therapy.

OBJECTIVE: To report 2 cases of hyperammonemic encephalopathy induced by sunitinib in patients with metastatic gastrointestinal stromal tumor (GIST). CASE SUMMARY: A 58-year-old man with imatinib-resistant metastatic GIST presented to the emergency department with confusion that developed 17 days after the initiation of sunitinib 50 mg/day. His serum ammonia level was markedly elevated (210 μg/dL). Sunitinib was discontinued, and an enema with lactulose was administered every hour. His neurologic status normalized within 24 hours and his serum ammonia level decreased to 64 μg/dL. A 68-year-old woman with imatinib-resistant metastatic GIST was admitted into the emergency department with confusion and irritability that developed 10 days after the start of sunitinib therapy. Her serum ammonia level was markedly elevated (389 μg/dL). Sunitinib was discontinued, and an enema with lactulose was administered every hour. Within 24 hours, her mental status was improved and her serum ammonia level was decreased to 116 μg/dL. Sunitinib was reintroduced, and the same symptoms occurred after day 7 of administration. Sunitinib was not prescribed afterward and the woman did not experience any further encephalopathic symptoms. DISCUSSION: Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases such as stem cell factor receptor, vascular endothelial growth factor, and platelet-derived growth factor. It is used as second-line therapy for patients with imatinib-resistant GIST. Hyperammonemic encephalopathy is an uncommon fatal complication of chemotherapy. According to the Naranjo probability scale, sunitinib was a probable cause of hyperammonemic encephalopathy in the patients described here. Although the mechanism of hyperammonemia is unclear, hyperammonemic encephalopathy might be caused by a vascular disorder related to the antiangiogenic properties of sunitinib, and it has ethnic differences associated with genetic polymorphisms. CONCLUSIONS: Sunitinib may induce hyperammonemic encephalopathy in some patients. Although further studies are warranted, clinicians should be aware of this severe adverse event when using sunitinib for treatment of GIST.