Partial sternectomy with reconstruction of a giant cell tumor of the sternum, a case report, Saudi, Arabia.

BACKGROUND: Giant cell tumor (GCT) is a relatively common and locally aggressive benign bone tumor that rarely affects the sternum. CASE PRESENTATION: We report a case of giant cell tumor of the sternum in a 28-year-old Saudi with painful swelling at the lower part of the sternum. Subtotal sternectomy and reconstruction with a neosternum using two layers of proline mesh, a methyl methacrylate prosthesis, and bilateral pectoralis muscle advancement flaps were performed. CONCLUSIONS: Giant cell tumor of the sternum is a rare diagnosis. Surgical resection with negative margins is the ideal management. To avoid defects or instability of the chest wall, reconstruction of the chest wall with neosternum should be considered.

The ARISCAT Risk Index as a Predictor of Pulmonary Complications After Thoracic Surgeries, Almoosa Specialist Hospital, Saudi Arabia.

Background: Pulmonary complications after thoracic surgery are common and are associated with prolonged hospital stay, higher costs, and increased mortality. This study aimed to evaluate the value of The Assess Respiratory risk in Surgical Patients in Catalonia (ARISCAT) risk index in predicting pulmonary complications after thoracic surgery. Methods: This retrospective study was conducted at Almoosa Specialist Hospital, Saudi Arabia, from August 2016 to August 2019 and included 108 patients who underwent thoracic surgery during the study period. Demographic data, ARISCAT risk index score, length of hospital stay, time of chest tube removal, postoperative complications, and time of discharge were recorded. Results: The study involved 108 patients who met the inclusion criteria. Their mean age was 42.5 ± 18.9 years, and most of them were men (67.6%). Comorbid diseases were present in 53.7%, including mainly type 2 diabetes mellitus and hypertension. FEV1% was measured in 58 patients, with a mean of 71.1 ± 7.3%. The mean ARISCAT score was 39.3 ± 12.4 and ranged from 24 to 76, with more than one-third (35.2%) having a high score grade. The most common surgical procedures were thoracotomy in 47.2%, video-assisted thoracoscopic surgery (VATS) in 28.7%, and mediastinoscopy in 17.6%. Postoperative pulmonary complications (PPCs) occurred in 22 patients (20.4%), mainly pneumonia and atelectasis (9.2%). PPCs occurred most frequently during thoracotomy (68.2%), followed by VATS (13.6%), and mediastinoscopy (9.1%). Multinomial logistic regression of significant risk factors showed that lower FEV1% (OR = 0.88 [0.79-0.98]; p=0.017), longer ICU length of stay (OR = 1.53 [1.04-2.25]; p=0.033), a higher ARISCAT score (OR = 1.22 [1.02-1.47]; p=0.040), and a high ARISCAT grade (OR = 2.77 [1.06-7.21]; p=0.037) were significant predictors of the occurrence of postoperative complications. Conclusion: ARISCAT scoring system, lower FEV1% score, and longer ICU stay were significant predictors of postoperative complications. In addition, thoracotomy was also found to be associated with PPCs.

Common Presentation of Uncommon Disease: Inflammatory myofibroblastic tumor of the lung, case report.

Background: Inflammatory myofibroblastic tumor (IMT) of the lung is a rare lung tumor, accounting for 0.7% of all lung tumors. They are usually benign, but can invade surrounding structures, undergo malignant transformation, recur, or even metastasize. Case report: We report a 44-year-old adult diabetic male from Saudi Arabia who had been suffering from cough with severe sputum and left shoulder pain for 2 weeks. Chest radiography (X-ray and computed tomography (CT)) revealed the presence of a mass lesion in the left lower upper lobe with central cavitation. The diagnosis of inflammatory myofibroblast lung tumor was confirmed by histological and immunohistochemical examination of the CT guided lung biopsy. The patient was successfully treated with surgical resection of the tumor by left limited thoracotomy with safety margin, and IMT was also documented. Conclusion: A high degree of suspicion of a solitary pulmonary mass is required for diagnosis and management of an inflammatory myofibroblastic lung tumor. The clinical and radiologic presentation of an inflammatory myofibroblastic tumor is nonspecific and the diagnosis is rarely made before surgical biopsy. Histologic and immunohistochemical examination is usually required to confirm the diagnosis and prevent recurrence.

Pharmacologic Therapies to Prevent Relapse of Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

Relapse is the main cause of mortality in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adverse cytogenetic or molecular risk factors, as well as refractory disease or persistent measurable residual disease (MRD) at the time of transplantation are associated with an increased risk of recurrence. Salvage therapy for AML relapse after allo-HSCT is often limited to chemotherapy, donor lymphocyte infusions and/or second transplants and is rarely successful. Effective post-transplant preventive intervention in high risk AML may be crucial. The most frequent and promising approach is the use of post-transplant maintenance with hypomethylating agents or with FLT3 tyrosine kinase inhibitors when the target is present. Moreover, IDH1/IDH2 inhibitors and BCL-2 inhibitors in combination with other strategies are promising approaches in the maintenance setting. Here we summarize the current knowledge about the preemptive and prophylactic use of pharmacologic agents after allo-HSCT to prevent relapse of AML.

FLT3 inhibitors in acute myeloid leukemia: ten frequently asked questions.

The FMS-like tyrosine kinase 3 (FLT3) gene is mutated in approximately one third of patients with acute myeloid leukemia (AML), either by internal tandem duplications (FLT3-ITD), or by a point mutation mainly involving the tyrosine kinase domain (FLT3-TKD). Patients with FLT3-ITD have a high risk of relapse and low cure rates. Several FLT3 tyrosine kinase inhibitors have been developed in the last few years with variable kinase inhibitory properties, pharmacokinetics, and toxicity profiles. FLT3 inhibitors are divided into first generation multi-kinase inhibitors (such as sorafenib, lestaurtinib, midostaurin) and next generation inhibitors (such as quizartinib, crenolanib, gilteritinib) based on their potency and specificity of FLT3 inhibition. These diverse FLT3 inhibitors have been evaluated in myriad clinical trials as monotherapy or in combination with conventional chemotherapy or hypomethylating agents and in various settings, including front-line, relapsed or refractory disease, and maintenance therapy after consolidation chemotherapy or allogeneic stem cell transplantation. In this practical question-and-answer-based review, the main issues faced by the leukemia specialists on the use of FLT3 inhibitors in AML are addressed.

Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for Fms-like tyrosine kinase 3-mutated acute myeloid leukemia.

BACKGROUND: Sorafenib has shown encouraging results in patients with Fms-like tyrosine kinase 3 (FLT3)-positive acute myeloid leukemia. Its role after allogeneic stem cell transplantation (HSCT) has been reported in a few cases with encouraging results. METHODS: The authors describe the use of sorafenib as a maintenance agent after HSCT in 27 patients with FLT3-positive acute myeloid leukemia. RESULTS: The median age of the patients was 46 years (range, 15-57 years). Sorafenib was introduced at a median of 70 days (range, 29-337 days) after HSCT. The median treatment duration was 8.4 months (range, 0.2-46 months). Eleven patients experienced treatment toxicities, mainly of grade 1 to 2 (graded according to the National Cancer Institute Common Toxicity Criteria [version 4.0]). Dose reduction or withdrawal was required in 4 patients and 4 patients, respectively. The persistence of toxicity prompted treatment withdrawal in 1 patient. Clinical improvement followed dose modifications. Thirteen patients experienced chronic graft-versus-host disease (limited in 9 patients and extensive in 4 patients), resulting in dose reduction in 5 patients followed by withdrawal in 1 of these individuals. At a median follow-up of 18 months (range, 4-48 months), 25 patients were alive (all of whom were in complete molecular remission) and 18 were still receiving treatment, with 1-year overall survival and progression-free survival rates of 92% ± 6% and 92% ± 5%, respectively. CONCLUSIONS: Sorafenib treatment after HSCT appears to be feasible and highly effective with dose individualization according to patient tolerability. Further analysis is needed to evaluate the immunomodulating role of sorafenib after HSCT. The data from the current support prospective controlled trials of sorafenib after HSCT. Cancer 2017;123:2867-74. © 2017 American Cancer Society.

Thymoma with Concomitant Pure Red Cell Aplasia, Good's Syndrome and Myasthenia Gravis Responding to Rituximab.

Thymomas are often associated with a variety of autoimmune diseases, mostly myasthenia gravis. The association of thymomas with both pure red cell aplasia (PRCA) and Good's syndrome is exceedingly rare. To the best of our knowledge, the combination of a thymoma with manifestations of myasthenia gravis, PRCA, and Good's syndrome, as in our case herein, has not been described before in the medical literature. We present a 90-year-old man initially diagnosed with an asymptomatic thymoma. Later, he developed generalized muscle weakness and was found to have severe anemia. He was diagnosed with PRCA, myasthenia gravis and Good's syndrome. He responded to rituximab with restoration of bone marrow erythroid maturation and stabilization of red blood cell counts.

TPOX Triallelic Genotype: An Interesting Pattern to Be Noted in Bone Marrow Transplantation Monitoring.

AIMS: TPOX triallelic genotypic pattern has been described in the setting of forensic and paternity testing but not in bone marrow transplantation (BMT) monitoring for graft engraftment. MATERIALS AND METHODS: A total of 50 cases have been studied using the AmpFLSTR(®) Identifiler™ polymerase chain reaction amplification kit as part of the workup of patients and donors before and after BMT at the American University of Beirut Medical Center. RESULTS: Of the 50 studied cases, 49 showed typical allelic patterns of the variable short tandem repeats detected by the assay; however, one single patient showed a biallelic TPOX genotype in the pre-BMT specimen but a triallelic pattern in the post-BMT sample. CONCLUSION: Triallelic patterns of TPOX should also be considered in the context of BMT monitoring testing where misinterpretation of the allelic pattern can lead to wrong unwanted conclusions related to the graft condition and proper quantification of donor DNA.

Sorafenib Maintenance Appears Safe and Improves Clinical Outcomes in FLT3-ITD Acute Myeloid Leukemia After Allogeneic Hematopoietic Cell Transplantation.

BACKGROUND: The FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) gene is one of the most frequently observed genetic alterations in acute myeloid leukemia (AML), with an incidence of about 20% to 30%. FLT3-ITD is significantly associated with a poor outcome, and offering an allogeneic hematopoietic cell transplantation (allo-HCT) is recommended for patients harboring this mutation. Sorafenib is a tyrosine kinase inhibitor active against RAF, VEGF, and FLT3-ITD. It has been used in an off-label fashion in FLT3-ITD AML. PATIENTS AND METHODS: We retrospectively assessed the successful use of sorafenib after allo-HCT in patients with FLT3-ITD AML. Six FLT3-ITD AML patients received sorafenib as posttransplantation maintenance therapy (n = 5) or as salvage therapy after a post-allo-HCT relapse (n = 1) and continued afterward. RESULTS: One patient developed myocardial infarction 100 days after initiation of sorafenib. Interestingly, skin graft versus host disease (grade II) was observed in 5 of 6 patients and generally occurred within few days after initiation of sorafenib, but it responded promptly to corticosteroid therapy in all patients. All 6 patients were alive and in complete remission at a median follow-up of 16 months (range, 10-29 months) since first induction and at a median follow-up of 12 months (range, 4-20 months) since initiation of sorafenib. Remarkably, the disease of all patients was in molecular remission. CONCLUSION: Sorafenib appears to be an effective maintenance therapy after allo-HCT in FLT3-ITD AML, with achievement of durable complete responses. This suggests an immunomodulatory effect of sorafenib in the posttransplantation setting and warrants a broader clinical evaluation of the use of maintenance sorafenib in FLT3-ITD AML.

Successful treatment of hydroxyurea-associated chronic leg ulcers associated with squamous cell carcinoma.

Hydroxyurea (HU) is an antineoplastic drug used in the treatment of chronic myeloproliferative neoplasms (MPNs). HU is associated with cutaneous adverse effects, whereas severe complications such as leg ulcers and non-melanoma skin cancers (NMSCs) are rare and only observed after long-term treatment. We herein report a patient with essential thrombocythemia (ET) treated chronically with HU, and who developed refractory bilateral leg ulcers complicated by squamous cell carcinoma (SCC) over both heels. The patient was successfully managed by multiple debridement stages and skin grafting surgeries.

Extracorporeal photopheresis in steroid-refractory acute or chronic graft-versus-host disease: results of a systematic review of prospective studies.

Acute and chronic graft-versus-host disease (GVHD) remain major obstacles for successful allogeneic hematopoietic cell transplantation. Extracorporeal photopheresis (ECP) modulates immune cells, such as alloreactive T cells and dendritic cells, and improves GVHD target organ function(s) in steroid-refractory GVHD patients. We performed a systematic review to evaluate the totality of evidence regarding the efficacy of ECP for treatment of acute and chronic steroid-refractory or steroid-dependent GVHD. Nine studies, including 1 randomized controlled trial, met inclusion criteria, with a total of 323 subjects. In pooled analyses, overall response rates (ORR) were .69 (95% confidence interval [CI], .34 to .95) and .64 (95% CI, .47 to .79) for acute and chronic GVHD, respectively. In acute GVHD organ-specific responses, ECP resulted in the highest ORR for cutaneous, with .84 (95% CI, .75 to .92), followed by gastrointestinal with .65 (95% CI, .52 to .78). Similar response rates were seen in chronic GVHD involving the skin and gastrointestinal tract. Conversely, ORR for chronic GVHD involving the lungs was only .15 (95% CI, 0 to .5). In chronic GVHD, grades 3 to 4 adverse events were reported at .38 (95% CI, .06 to .78). ECP-related mortality rates were extremely low. Rates of immunosuppression discontinuation were .55 (95% CI, .40 to .70) and .23 (95% CI, .07 to .44) for acute and chronic GVHD, respectively. In summary, albeit limited by numbers of available studies, pooled analyses of prospective studies demonstrate encouraging responses after ECP treatment in acute and chronic GVHD after failing corticosteroids. Further research efforts are needed to improve organ-specific responses.

Significance of the use of the ViennaLab "Cardiovascular Disease panel" (CVD) Assay as a reflex test for the "Factor V/II/MTHFR Assay".

INTRODUCTION: Trends toward identifying risk factors of thrombotic complications had become essential as an attempt to prevent and decrease the incidence of the complications. Thrombosis has been associated with predisposing factors like mutations in FV, PTH, MTHFR and other genes. AIM: Evaluate whether the CVD StripAssay has an added value in the screening for more thrombophilia risk factors, which may predispose for the development of cardiovascular diseases and other thrombotic clinical conditions. METHODS: We compared the results for 94 patients who were previously tested for Factor V, Factor II and MTHFR gene mutations using the ViennaLab FV-PTH-MTHFR StripAssay, and for whom additional testing for the Cardiovascular Disease panel (CVD StripAssay, ViennaLab) was requested. RESULTS: Using the CVD StripAssay, 66% of patients who had no mutations when tested using the FV-PTH-MTHFR StripAssay or carried a mutation for MTHFR, were found to have additional genes' SNPs or mutations that are highly associated with a risk of thrombosis as per the available international literature. CONCLUSION: This observation is of extreme importance in clinical practice for the introduction of the extended CVD panel into routine molecular diagnostic test menus and highlights the importance of genetic analysis of the implicated genes in the management of patients with a thrombotic episode presentation.