The Extraordinary Case of a Woman with a 30-Year-Long Diffuse Leishmaniasis Cured with One Single Ampoule of Intranasal Pentavalent Antimoniate.

Infection with Leishmania amazonensis and L. mexicana may lead to diffuse cutaneous leishmaniasis. The cure is exceptional, especially for the strange case of this lady. Case report: The patient acquired the disease in childhood and remained with lesions for over 30 years, albeit several treatments. She worsened after a pregnancy, developing disseminated lesions. Miltefosine with amphotericin B and pentamidine resulted in remission. Lesions reappeared after one year, accompanied by intra-nasal infiltration of the disease. The nasal spraying of a single ampoule of pentavalent antimoniate resulted in the sustained disappearance of the nasal symptoms and all the cutaneous lesions. After over eight years, she remains disease-free, albeit under renal replacement therapy. The high nasal mucosal antimonial concentration may explain the long-lasting cure via new MHC class I epitope-specific CD8+ cell clones against L. amazonensis present in the nasal mucosa.

Nivolumab in Metastatic Adrenocortical Carcinoma: Results of a Phase 2 Trial.

CONTEXT: Systemic treatment of metastatic adrenocortical carcinoma (ACC) remains limited to chemotherapy and mitotane. Preliminary evidence suggesting that antitumor immune responses can be elicited in ACC has fostered interest in checkpoint inhibitors such as anti-PD-1 nivolumab. OBJECTIVE: The primary endpoint was objective response rate according to the response evaluation criteria in solid tumors. Secondary endpoints were progression-free survival (PFS), overall survival, and safety. DESIGN: Single-arm, multicenter, phase 2 clinical trial with two-stage design. SETTING: Comprehensive cancer center. PATIENTS: Ten adult patients with metastatic ACC previously treated with platinum-based chemotherapy and/or mitotane as well as patients who declined front-line chemotherapy. INTERVENTION: Nivolumab (240 mg) IV every 2 weeks. RESULTS: Ten patients with metastatic ACC were enrolled between March and December 2016. The median number of doses of nivolumab administered was two. Three patients only received one treatment [one died of disease progression, one discontinued due to adverse events (AEs), one withdrew after beginning treatment]. The median PFS was 1.8 months. The median follow-up was 4.5 months (range, 0.1 to 25.6 months). Two patients had stable disease for a duration of 48 and 11 weeks, respectively. One patient had an unconfirmed partial response but discontinued the study due to an AE. Most AEs were grade 1/2. The most common grade 3/4 treatment-related AEs were aspartate aminotransferase and alanine aminotransferase elevations, mucositis, and odynophagia. CONCLUSION: Nivolumab demonstrated modest antitumor activity in patients with advanced ACC. The nivolumab safety profile was consistent with previous clinical experience without any unexpected AEs in this population.

Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer.

INTRODUCTION: Anaplastic lymphoma kinase (ALK) inhibitors are the mainstay treatment for patients with non-small cell lung carcinoma (NSCLC) harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in different indications, their toxicity profile warrants an update. MATERIALS AND METHODS: A systematic literature search was performed in July 2017. Studies evaluating US FDA approved doses of one of the following ALK inhibitors: Crizotinib, Ceritinib, Alectinib or Brigatinib as monotherapy were included. Data were analyzed using random effects meta-analysis for absolute risks (AR), study heterogeneity, publication bias and differences among treatments. RESULTS: Fifteen trials with a total of 2,005 patients with evaluable toxicity data were included in this report. There was significant heterogeneity amongst different studies. The pooled AR of death and severe adverse events were 0.5% and 34.5%, respectively. Grade 3/4 nausea, vomiting, diarrhea, and constipation were uncommon: 2.6%, 2.5%, 2.7%, 1.2%, respectively. CONCLUSIONS: ALK inhibitors have an acceptable safety profile with a low risk of treatment-related deaths. Important differences in toxicity profile were detected amongst the different drugs.

An Extremely Rapid Case of Pneumonitis with the Use of Nivolumab for Pancreatic Adenocarcinoma.

Pancreatic cancer is the fourth most common cancer death in the United States despite comprising a small percentage of the total number of cancer cases. The estimated 5-year overall survival (OS) for patients with distant metastatic disease is approximately 3%. New treatment options are an unmet need and remain an area of active investigation. A 53-year-old male with metastatic pancreatic cancer presented to the hospital with acute-on-chronic respiratory failure approximately 24 hours after receiving a novel therapeutic combination. Chest imaging showed marked changes as concerning for pneumonitis. Infectious workup was negative. The patient had initial clinical improvement after receiving initial intravenous steroids and oxygen support but eventually deteriorated later opting for supportive measures only. With infection ruled out, drug-induced pneumonitis was felt to be the likely cause of the radiologic and clinical changes. The rapidity of onset of symptoms is the aspect being highlighted in this case.

Anaplastic Lymphoma Kinase Mutation (ALK F1174C) in Small Cell Carcinoma of the Prostate and Molecular Response to Alectinib.

Purpose: Small cell carcinoma of the prostate (SCCP) is an aggressive disease that can arise de novo or by transdifferentiation from prostate adenocarcinoma. Alterations in anaplastic lymphoma kinase (ALK) gene are involved in neuroblastoma, lung cancer, and other malignancies, but its role in SCCP has not been documented. We describe a patient with refractory de novo SCCP with ALK F1174C-activating mutation who obtained clinical benefit from treatment with ALK inhibitor.Experimental Design: Next-generation sequencing (NGS) was used to analyze primary and circulating tumor DNA (ctDNA). Prostate cancer databases were queried for alterations in ALK gene, mRNA, and its impact in clinical outcomes. In vitro prostate cell line/organoid models were generated by lentiviral-mediated expression of ALK and ALK F1174C and assessed for response to ALK inhibitors crizotinib and alectinib.Results: NGS analysis of the primary tumor and ctDNA of a 39-year-old patient with refractory SSCP identified ALK F1174C mutation. Treatment with second-generation ALK inhibitor alectinib resulted in radiographic stable disease for over 6 months, symptomatic improvement, and significant molecular response as reflected by declining ctDNA allele fraction. Analysis of prostate cancer datasets showed that ALK amplification was associated with poor outcome. In prostate cancer cells and organoids, ALK F1174C expression enhanced growth and induced expression of the neuroendocrine marker neuron-specific enolase. Alectinib was more effective than crizotinib in inhibiting ALK F1174C-expressing cell growth.Conclusions: These findings implicate ALK-activating mutations in SCCP pathogenesis and suggest the therapeutic potential of targeting ALK molecular alterations in some patients with SCCP. Clin Cancer Res; 24(12); 2732-9. ©2018 AACR.

A Rare Case of Glioblastoma Multiforme with Osseous Metastases.

Glioblastoma multiforme is the most common malignant primary central nervous system neoplasm in adults. It has a very aggressive natural history with a median overall survival estimated at 14.6 months despite multimodality treatment. Extracranial metastases are very rare with few case reports published to date. We report the case of a 65-year-old male who underwent maximal safe resection for a newly diagnosed brain mass after presentation with new neurologic symptoms. He then received standard postsurgical adjuvant treatment for glioblastoma. Subsequently, he underwent another resection for early progressive disease. Several months later, he was hospitalized for new-onset musculoskeletal complaints. Additional investigation revealed new metastatic osseous lesions which were initially felt to be a new malignancy. The patient opted for supportive care and died 12 days later. Despite choosing no treatment, he elected to undergo a bone biopsy to understand the new underlying process. Results were that of metastatic GBM and were reported after the patient expired. Physicians caring for patients with GBM and new nonneurologic symptoms may contemplate body imaging.

Analyses of selected safety endpoints in phase 1 and late-phase clinical trials of anti-PD-1 and PD-L1 inhibitors: prediction of immune-related toxicities.

PURPOSE: Anti-PD1 and PD-L1 antibodies are associated with immune-related adverse effects (irAEs). This analysis aims to assess the discrepancies between frequencies of irAEs observed in phase 1 trials with those seen in late-phase trials and to evolve the field of drug development. METHODS: PubMed search was conducted for articles published until December of 2016. Trials needed to have at least one of the study arms consisting of nivolumab, pembrolizumab or atezolizumab monotherapy. Trials were matched based on compound used and similarity of populations. All toxicities were reported as frequencies and percentages. P-values to assess differences between matches and non-matches of phase 1 and late-phase trials and between early and late-phase trials themselves were obtained via Fisher's exact test. Odds ratios were obtained via logistic regression. RESULTS: Our search yielded 15 late-phase and 10 matching phase 1 trials; n = 4823 and n = 1650, respectively. The most common AEs seen in phase 1 trials were also observed in late-phase trials except for phase 1 trials (median n = 118) with < 118 patients (P = 0.048). Rash, pruritus, and diarrhea were the most frequently irAEs reported. Only colitis was more frequent in late-phase studies (P = 0.045). CONCLUSION: Toxicities of anti-PD-1 and PD-L1 observed in phase 1 trials and late-phase trials are similar. There is positive correlation between phase 1 trial sample size and concordance of toxicity frequencies seen in late-phase studies. In conclusion, current immunotherapy phase 1 trials are appropriate in assessing safety profile of anti-PD-1 and PD-L1 antibodies.

Interstitial Pneumonitis Secondary to Trastuzumab: A Case Report and Literature Review.

Interstitial lung disease is a rare complication of trastuzumab-based breast cancer treatment with few case reports published. Herein, we report the case of a 67-year-old female with early-stage HER2-postitive breast cancer who developed interstitial pneumonitis during cycle 5 of treatment with trastuzumab combined with carboplatin and docetaxel. After supportive care and treatment with prednisone, the patient showed rapid improvement of respiratory symptoms. Retreatment with trastuzumab as a single agent led to worsening of symptoms and required a second course of treatment with prednisone combined with cyclophosphamide, which was followed by improvement of symptoms. In conclusion, interstitial pneumonitis is a rare but life-threatening adverse event from trastuzumab breast cancer treatment.

Follicular lymphoma presenting with leptomeningeal disease.

Follicular lymphoma is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. Central nervous system metastasis is a very rare complication portending a very poor prognosis. We report a rare case of follicular lymphoma presenting with leptomeningeal involvement achieving a complete remission after initial therapy.

Reversible posterior encephalopathy syndrome secondary to sunitinib.

Reversible posterior leukoencephalopathy syndrome (RPLS) is clinical radiologic condition associated with neurological symptoms and cerebral white matter edema. It has been associated with uncontrolled hypertension, eclampsia, immunosuppressants, and more recently the use of antiangiogenic drugs. Sunitinib is an inhibitor of the vascular endothelial growth factor receptor widely used in the treatment of metastatic renal cell carcinoma (RCC). We report a rare case of RPLS occurring on therapy with sunitinib in a patient with RCC. Our aim is to highlight the importance of considering RPLS as a diagnostic possibility and to hold sunitinib for RCC patients presenting with neurologic symptoms.

Adenocarcinoma of the lung presenting with atypical cystic brain lesions.

Brain metastases occur in up to 10-30% of patients with cancer. Metastatic lesions are usually diagnosed as multiple mass lesions at the junction of the grey and white matter with associated perilesional vasogenic oedema. Cysticercosis is an endemic disease in underdeveloped countries of Africa, Central and South America and is the most common parasitic infection of the central nervous system. The classical radiological finding of neurocysticercosis is cystic lesions showing the scolex in the brain parenchyma. We report a case of metastatic adenocarcinoma of the lung presenting with cystic brain lesions mimicking neurocysticercosis.

Metastatic insulinoma managed with radiolabeled somatostatin analog.

Insulinoma is a rare pancreatic neuroendocrine tumor. Overproduction of insulin and associated hypoglycemia are hallmark features of this disease. Diagnosis can be made through demonstration of hypoglycemia and elevated plasma levels of insulin or C-Peptide. Metastatic disease can be detected through computerized tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT. Somatostatin receptor scintigraphy can be used not only to document metastatic disease but also as a predictive marker of the benefit from therapy with radiolabeled somatostatin analog. Unresectable metastatic insulinomas may present as a major therapeutic challenge for the treating physician. When feasible, resection is the mainstay of treatment. Prevention of hypoglycemia is a crucial goal of therapy for unresectable/metastatic tumors. Diazoxide, hydrochlorothiazide, glucagon, and intravenous glucose infusions have been used for glycemic control yielding temporary and inconsistent results. Sandostatin and its long-acting depot forms have occasionally been used in the treatment of Octreoscan-positive insulinomas. Herein, we report a case of metastatic insulinoma with very difficult glycemic control successfully treated with the radiolabeled somatostatin analog lutetium ((177)LU).

Successful plasma exchange combined with rituximab therapy in aggressive APS-related cutaneous necrosis.

Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disorder characterized by venous and/or arterial thrombosis or recurrent fetal loss associated with the presence of antiphospholipid antibodies and/or a lupus anticoagulant. The skin appears to be an important target organ and many cases of APS may present with skin manifestations. These lesions may be manifold and may take the form of livedo reticularis, livedo racemosa, ulcerations, digital gangrene, subungeal splinter hemorrhages, superficial venous thrombosis, thrombocytopenic purpura, pseudovasculitic manifestations, extensive cutaneous necrosis, or primary anetoderma. We report a case of fulminant APS-related cutaneous necrosis. A 38-year-old Caucasian male with a past history of APS, multiple deep vein thrombi/pulmonary emboli, presented with necrotic lesions on his right upper and right lower extremities. Initially, baseline anticoagulation was increased without improvement. Subsequently, plasma exchange was initiated on a daily schedule. Furthermore, rituximab 1,000 mg IV was administered on days 1 and 15. After six consecutive daily sessions of plasma exchange, there was significant regression of the necrotic lesions. After a 22-day hospital stay, the patient was discharged to home on fondaparinux. The patient presented approximately 2 months later after missing follow-up appointments. At the time, his initial lesions looked remarkably improved.

Activity of azacitidine in chronic myelomonocytic leukemia.

BACKGROUND: Hypomethylating drugs are useful in the management of myelodysplastic syndrome (MDS). Two of these drugs, azacitidine and decitabine, have received FDA approval for the treatment of MDS and chronic myelomonocytic leukemia (CMML). However, phase 2 and 3 studies that assessed these agents in MDS included only a small number of patients with CMML. The objective of this study was to evaluate the efficacy and safety of azacitidine in the treatment of CMML. METHODS: The records of thirty-eight patients diagnosed with CMML and treated with azacitidine at our institution were reviewed. Azacitidine was administered at 75 mg/m(2) /day for 7 days or 100 mg/m(2) /day for 5 days every 4 weeks. Patients who received at least 1 cycle of the drug were considered evaluable for response. RESULTS: Response was assessed by the modified International Working Group (IWG) criteria. The overall response rate was 39% (14 of 36); complete response (CR) rate was 11% (4 of 36); partial response (PR) rate was 3% (1 of 36); hematologic improvement (HI) was 25% (9 of 36). The median overall survival was 12 months. There was a statistically significant overall survival advantage in responders compared with nonresponders: 15.5 months versus 9 months, respectively (P = .04). Treatment was generally well tolerated. One of 2 patients had complete resolution of a skin rash that was due to monocytic infiltration. CONCLUSIONS: Azacitidine is active in the treatment of CMML. The therapy-associated toxicity is acceptable. Our results support further investigation of azacitidine in CMML, particularly in combination with other agents.

Early determinants of death due to multiple organ failure after noncardiac surgery in high-risk patients.

BACKGROUND: Prediction of perioperative cardiac complications is important in the medical management of patients undergoing noncardiac surgery. However, these patients frequently die as a consequence of primary or secondary multiple organ failure (MOF), often as a result of sepsis. We investigated the early perioperative risk factors for in-hospital death due to MOF in surgical patients. METHODS: This was a prospective, multicenter, observational cohort study performed in 21 Brazilian intensive care units (ICUs). Adult patients undergoing noncardiac surgery who were admitted to the ICU within 24 hours after operation were evaluated. MOF was characterized by the presence of at least 2 organ failures. To determine the relative risk (RR) of in-hospital death due to MOF, we performed a logistic regression multivariate analysis. RESULTS: A total of 587 patients were included (mean age, 62.4 ± 17 years). ICU and hospital mortality rates were 15% and 20.6%, respectively. The main cause of death was MOF (53%). Peritonitis (RR 4.17, 95% confidence interval [CI] 1.38-12.6), diabetes (RR 3.63, 95% CI 1.17-11.2), unplanned surgery (RR 3.62, 95% CI 1.18-11.0), age (RR 1.04, 95% CI 1 0.01-1.08), and elevated serum lactate concentrations (RR 1.52, 95% CI 1.14-2.02), a high central venous pressure (RR 1.12, 95% CI 1.04-1.22), a fast heart rate (RR 3.63, 95% CI 1.17-11.2) and pH (RR 0.04, 95% CI 0.0005-0.38) on the day of admission were independent predictors of death due to MOF. CONCLUSIONS: MOF is the main cause of death after surgery in high-risk patients. Awareness of the risk factors for death due to MOF may be important in risk stratification and can suggest routes for therapy.

Estudo da estabilidade da coluna lombar após facetectomia / Estudio de la estabilidad de la columna lumbar después de la facetectomía / The study of lumbar spine's stability after facetectomy

OBJETIVO: determinar a presença, ou não, de instabilidade lombar após a realização de facetectomia total unilateral para a descompressão radicular. MÉTODOS: os autores realizaram uma análise retrospectiva por avaliação clínica e radiográfica de 29 pacientes operadores, por discopatia, durante o período de janeiro de 1985 até janeiro de 1995. Os pacientes apresentavam queixa de dor ciática aguda, sem dor lombar prévia, e foram submetidos à facetectomia total unilateral para a descompressão radicular. Os casos operados por esta técnica necessitaram de manipulações excessivas com riscos de lesão da raiz nervosa. RESULTADOS: após um seguimento que variou de 9 a 17 anos, os resultados foram excelentes em 17 pacientes, bom em 9, regular em 3. CONCLUSÃO: nessa série de casos, a facetectomia total unilateral não foi fator determinante de instabilidade lombar.

OBJECTIVE: to determine the presence or absence of lumbar instability after the execution of unilateral total facetectomy for the root decompression. METHODS: the authors made a retrospective review by clinical and radiological evaluation of 29 discopathy operated patients, during the period from January 1985 to January 1995. These patients presented acute sciatica without previous lumbar pain, and they were submitted to unilateral total facetectomy for the radicular decompression. In this series, all cases needed an excessive manipulation and were under the risks of root lesion. RESULTS: after a follow-up that varied from 9 to 17 years old, the results were excellent for 17 patients, good for 9 and regular for 3. CONCLUSION: in these cases, unilateral total facetectomy was not a determinant factor of lumbar instability.

OBJETIVO: determinar la presencia o no de la inestabilidad lumbar después de la realización de facetectomía total unilateral para la descompresión radicular. MÉTODOS: los autores realizaron un análisis retrospectivo por evaluación clínica y radiográfica de 29 pacientes operados por discopatía, durante el periodo de Enero de 1985 hasta Enero de 1995. Los pacientes presentaban queja de dolor ciática aguda, sin dolor lumbar previa y fueron sometidos a la facetectomía total unilateral para la descompresión radicular. Los casos operados por esta técnica necesitaron de manipulaciones excesivas con riesgo de lesión de la raíz nerviosa. RESULTADOS: después de un seguimiento que varió de 9 a 17 años, los resultados fueron excelentes en 17 pacientes, bueno en 9 y regular en 3. CONCLUSIÓN: en esa serie de casos la facetectomía total unilateral no fue factor determinante de inestabilidad lumbar.

Ethics roundtable debate: patients and surrogates want 'everything done'--what does 'everything' mean?

Highly complex and specialized care plans sometimes overwhelm the comprehension of patients and families. Many optimistic surrogates of critically ill patients err on the side of desiring that everything be done but with a nebulous idea of what 'everything' entails. Physicians must work closely to educate surrogates as to the benefits versus the risks of treatment. Our roundtable experts ponder the question of whether providers possess the authority to interpret unilaterally the nature of requests for everything.

Análise crítica das mensurações pré e pós operatória nas mamoplastias redutoras / Critical analysis the mesurations daily pay and after operatory in the mamoplasty reducing

A mamoplastia redutora promove várias alterações na forma e volume da glândula mamária. A mudança de posicionamento no tórax de maneira satisfatória para a maioria das pacientes, permitindo resultado estético almejado. A redução da mama apresentou resultados de cicatrizes que puderam ser correlacionados com algumas medidas pré determinadas como a base, a altura, a distância da clavícula-mamilo e distância fúcula sulco. Foram operadas 40 pacientes brancas com idade que variou de 14 a 51 anos.