Citations

Giant-cell tumor of the bone (GCTB) is a rare neoplasm that affects young adults. The tumor is generally benign but sometimes can be locally aggressive. There are no standardized approaches to the treatment of GCTB. Recently, the RANKL inhibitor denosumab has shown activity in this tumor type. We present the case of a young female who presented with locally advanced disease and was successfully managed with the neoadjuvant use of denosumab allowing for surgical resection of the tumor that was previously deemed unresectable. Following surgery, the patient is being managed with continued use of denosumab as ‘maintenance,’ and she continues to be free of disease. Our case highlights a novel approach for the management of locally advanced and aggressive giant cell tumor of the bone.

SummaryPatients with aggressive non‐Hodgkin lymphoma (NHL) who relapse after autologous stem cell transplantation (ASCT) have a poor prognosis. Additional therapy is often poorly tolerated, and new treatment modalities are needed. This efficacy and safety study was a retrospective analysis of two phase II trials (NHL‐002 and NHL‐003) that studied single‐agent lenalidomide in patients with relapsed/refractory aggressive NHL with prior (n = 87) compared with no prior ASCT (n = 179). The overall response rate in the ASCT group was 39% [14% complete response (CR)], including 29% in patients with diffuse large B‐cell lymphoma, 63% in mantle cell lymphoma, and 60% in transformed lymphoma. The timing of transplant relative to receiving lenalidomide had no effect on outcomes. Median progression‐free survival for the ASCT group was 3·7 months (16·9 months for patients in CR; 7·3 months for partial responders) at a median 12·5‐month follow‐up. Median response duration was 7·9 months. Regardless of prior ASCT, lenalidomide monotherapy was efficacious in heavily pretreated patients with aggressive, relapsed/refractory NHL, with a safety profile that was consistent with prior studies of single‐agent lenalidomide.

Consensus abstract Background The management of primary rectal cancer beyond total mesorectal excision planes (PRC-bTME) and recurrent rectal cancer (RRC) is challenging. There is global variation in standards and no guidelines exist. To achieve cure most patients require extended, multivisceral, exenterative surgery, beyond conventional total mesorectal excision planes. The aim of the Beyond TME Group was to achieve consensus on the definitions and principles of management, and to identify areas of research priority. Methods Delphi methodology was used to achieve consensus. The Group consisted of invited experts from surgery, radiology, oncology and pathology. The process included two international dedicated discussion conferences, formal feedback, three rounds of editing and two rounds of anonymized web-based voting. Consensus was achieved with more than 80 per cent agreement; less than 80 per cent agreement indicated low consensus. During conferences held in September 2011 and March 2012, open discussion took place on areas in which there is a low level of consensus. Results The final consensus document included 51 voted statements, making recommendations on ten key areas of PRC-bTME and RRC. Consensus agreement was achieved on the recommendations of 49 statements, with 34 achieving consensus in over 95 per cent. The lowest level of consensus obtained was 76 per cent. There was clear identification of the need for referral to a specialist multidisciplinary team for diagnosis, assessment and further management. Conclusion The consensus process has provided guidance for the management of patients with PRC-bTME or RRC, taking into account global variations in surgical techniques and technology. It has further identified areas of research priority.

Consensus abstract Background The management of primary rectal cancer beyond total mesorectal excision planes (PRC-bTME) and recurrent rectal cancer (RRC) is challenging. There is global variation in standards and no guidelines exist. To achieve cure most patients require extended, multivisceral, exenterative surgery, beyond conventional total mesorectal excision planes. The aim of the Beyond TME Group was to achieve consensus on the definitions and principles of management, and to identify areas of research priority. Methods Delphi methodology was used to achieve consensus. The Group consisted of invited experts from surgery, radiology, oncology and pathology. The process included two international dedicated discussion conferences, formal feedback, three rounds of editing and two rounds of anonymized web-based voting. Consensus was achieved with more than 80 per cent agreement; less than 80 per cent agreement indicated low consensus. During conferences held in September 2011 and March 2012, open discussion took place on areas in which there is a low level of consensus. Results The final consensus document included 51 voted statements, making recommendations on ten key areas of PRC-bTME and RRC. Consensus agreement was achieved on the recommendations of 49 statements, with 34 achieving consensus in over 95 per cent. The lowest level of consensus obtained was 76 per cent. There was clear identification of the need for referral to a specialist multidisciplinary team for diagnosis, assessment and further management. Conclusion The consensus process has provided guidance for the management of patients with PRC-bTME or RRC, taking into account global variations in surgical techniques and technology. It has further identified areas of research priority.

PurposeTo quantify the two principal forms of hepatic storage iron, diffuse, soluble iron (primarily ferritin), and aggregated, insoluble iron (primarily hemosiderin) using a new MRI method in patients with transfusional iron overload.Materials and MethodsSix healthy volunteers and 20 patients with transfusion‐dependent thalassemia syndromes and iron overload were examined. Ferritin‐ and hemosiderin‐like iron were determined based on the measurement of two distinct relaxation parameters: the “reduced” transverse relaxation rate, RR2, and the “aggregation index,” A, using three sets of Carr‐Purcell‐Meiboom‐Gill (CPMG) datasets with different interecho spacings. Agarose phantoms, simulating the relaxation and susceptibility properties of tissue with different concentrations of dispersed (ferritin‐like) and aggregated (hemosiderin‐like) iron, were used for validation.ResultsBoth phantom and in vivo human data confirmed that transverse relaxation components associated with the dispersed and aggregated iron could be separated using the two‐parameter (RR2, A) method. The MRI‐determined total hepatic storage iron was highly correlated (r = 0.95) with measurements derived from biopsy or biosusceptometry. As total hepatic storage iron increased, the proportion stored as aggregated iron became greater.ConclusionThis method provides a new means for noninvasive MRI determination of the partition of hepatic storage iron between ferritin and hemosiderin in iron overload disorders. J. Magn. Reson. Imaging 2014;39:307–316. © 2013 Wiley Periodicals, Inc.

Abstract Acute eosinophilic pneumonia is characterized by acute respiratory insufficiency, hypoxemia, fever, diffuse radiographic infiltrates, and eosinophilia in bronchoalveolar lavage fluid (BALF) or lung biopsies in the absence of infection, atopy, or asthma. A rapid response to corticosteroids is characteristic. We reviewed our experience with nine cases of acute lung disease with histologic features of acute and organizing diffuse alveolar damage and prominent interstitial and alveolar eosinophils in order to determine whether this pathology was characteristic of acute eosinophilic pneumonia. The mean age of the patients (four men and five women) was 53 yr (range: 33 to 71 yr). They presented with 2 to 21 d of dyspnea, cough, myalgias, and fever. All were hypoxic and had bilateral infiltrates on chest radiographs. Peripheral blood eosinophilia was present in four of eight patients (peripheral blood count unavailable for one patient). All patients were treated with high-dose corticosteroids with a mean time to symptomatic and radiographic improvement of 4 d. Seven of the nine patients enrolled in the study are alive without relapse; one patient has a mild deficit in diffusing capacity, and one patient died of a myocardial infarct while improving on therapy. The presence of eosinophils in cases of acute respiratory insufficiency due to diffuse alveolar damage (DAD) should suggest the diagnostic possibility of acute eosinophilic pneumonia. Acute eosinophilic pneumonia should be distinguished from other causes of DAD because of important differences in natural history.

Abstract Cyclophosphamide-induced lung toxicity may be difficult to recognize because of the presence of confounding variables such as concomitant use of other cytotoxic drugs, opportunistic infections, diffuse pulmonary malignancy, radiation pneumonitis, and oxygen toxicity. The purpose of this retrospective analysis was to identify the clinical spectrum of pulmonary toxicity of cyclophosphamide. In our review of case records, we sought to identify patients in whom cyclophosphamide was the only identifiable etiologic factor for lung toxicity. In a 20-yr period six patients were identified with cyclophosphamide-induced lung disease, including five men and one woman ranging in age from 42 to 78 yr. Clinical features of toxicity include dyspnea, fever, cough, new parenchymal infiltrates, gas exchange abnormalities on pulmonary function tests, and pleural thickening on chest roentgenogram. Two patterns of cyclophosphamide-induced lung toxicity were identified. A single patient presented with early-onset pneumonitis and responded to discontinuation of the drug. Five patients with late-onset pneumonitis developed progressive pulmonary fibrosis associated with bilateral pleural thickening. Patients with late-onset pneumonitis showed no response to cessation of cyclophosphamide and institution of corticosteroid therapy. Three of these patients died of respiratory failure. Careful review of the individual cases reported in the literature as cyclophosphamide lung toxicity revealed only 12 cases in whom none of the additional confounding factors could be identified. These could easily be divided in the same two categories. Early-onset pneumonitis is reversible and may respond to corticosteroid therapy. Late-onset pneumonitis, frequently associated with pleural thickening, is clinically distinct from idiopathic pulmonary fibrosis but has a chronically progressive course. It appears unresponsive to corticosteroid therapy.

Abstract Pulmonary lymphangioleiomyomatosis (LAM) is an uncommon disease reported to occur exclusively in women. We describe a phenotypically normal man with pulmonary LAM. Fluorescence in situ hybridization (FISH) studies performed on the lung biopsy confirmed a normal XY genotype. Our patient also had stigmata of tuberous sclerosis complex (TSC), including facial angiofibromas and renal angiomyolipoma. Immunohistochemical stains of both LAM and renal angiomyolipoma showed positive immunoreactivity for hamartin (TSC1) and loss of immunoreactivity for tuberin (TSC2). Loss of heterozygosity (LOH) for TSC2 was further demonstrated in the renal angiomyolipoma. Coupled with the results of immunostains, these findings are consistent with TSC2 mutation.