Management of Diaphragm Tumors.

Diaphragm tumors are very rare, with secondary tumors being more common than primary tumors. The most common benign primary tumors include lipomas and cysts, and malignant primary tumors include rhabdomyosarcoma and leiomyosarcoma. Endometriosis is the most common benign secondary tumor, followed by malignant tumors with localized spread of disease. In addition, widely metastatic disease has been described. Benign lipomas and cysts can be managed conservatively, but more complex or concerning disease typically requires resection. The diaphragm can often be repaired primarily, though any large defect or tension would indicate the need for mesh or an autologous reconstruction.

Estudio clínico, radiológico y derivación en tumores musculoesqueléticos / Diagnosis and referral of musculoskeletal tumors

Musculoskeletal tumors are uncommon. However, the true burden of all bone and soft tissue tumors of extremities is underestimated. Usually, the diagnosis of sarcomas is missed or delayed. Therefore, an adequate clinical and radiological assessment, along with the awareness and application of simple guidelines for referral to a specialized center, are of utmost importance. These are critical steps for an appropriate diagnosis and treatment of sarcomas, improving their prognosis.

Use of Neoadjuvant Chemotherapy in Elderly Patients With Muscle-Invasive Bladder Cancer: A Population-Based Study, 2006-2017.

Objectives/Introduction Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is associated with survival benefit across patients of all ages, yet it is not offered to many elderly patients. We aimed to evaluate age-based disparity in treatment and outcomes of MIBC. Methods Using the National Cancer Database, we identified patients with MIBC from 2006 to 2017. Use of treatment modalities was compared between age groups. A second analysis compared perioperative outcomes and overall survival (OS) in elderly patients (70 years or older) undergoing RC with NAC vs no NAC. Propensity score weighting (PSW) was used for each analysis. Results In 70,911 patients, use of NAC with RC was lower in patients 70 years or older (7.2% vs 20.9%; P < .001). In patients 70 years or older undergoing RC, NAC was associated with shorter inpatient stay (8.5 vs 9.6 days; P < .001), decreased 30-day readmission (8.6% vs 10.6%; P <.001), and lower 30- and 90-day mortality (1.5% vs 3.1%; P = .01; and 4.9% vs 7.7%; P = .003, respectively). On weighted multivariate regressions, NAC predicted shorter length of stay and lower 30-and 90-day mortality. Elderly patients receiving NAC had improved OS compared with RC alone (P = .0011, 2010-2013; P < .001, 2014-2016). Conclusions Despite increased omission of NAC in patients 70 years or older, elderly patients receiving NAC and RC had improved perioperative outcomes and OS compared with those undergoing RC alone. There may be selection bias unaccounted for with our PSW; however, our results provide compelling evidence that NAC does not compromise surgical outcomes in appropriately selected elderly patients. Patients of advanced age who are candidates for RC should be offered NAC.

[Diagnosis and referral of musculoskeletal tumors]. / Estudio clínico, radiológico y derivación en tumores musculoesqueléticos.

Musculoskeletal tumors are uncommon. However, the true burden of all bone and soft tissue tumors of extremities is underestimated. Usually, the diagnosis of sarcomas is missed or delayed. Therefore, an adequate clinical and radiological assessment, along with the awareness and application of simple guidelines for referral to a specialized center, are of utmost importance. These are critical steps for an appropriate diagnosis and treatment of sarcomas, improving their prognosis.

An unusual extranodal natural killer/T-cell lymphoma presenting as chronic laryngitis: A case report.

RATIONALE: Nasal-type, extranodal natural killer (NK)/T-cell lymphoma is a rare lymphoma. The tumor usually shows ulcerative and necrotic lesions in the nasal cavities and sinuses. Tissue involvement outside the nasal cavity is uncommon. PATIENT CONCERN: We describe a 30-year-old man with a 2-month history of hoarseness, weight loss, and dyspnea. DIAGNOSIS: Magnetic resonance image (MRI) showed edema of the larynx with obliteration of the airway. Laryngoscopic examination described necrotic tissue in the glottis and larynx. The biopsy showed chronic, necrotizing laryngitis, with no granulomas, vasculitis, or atypical cells. The immunologic and microbiologic study was negative. Later, after immunosuppressive therapy, the patient presented erythema and diffuse enlargement of the right arm. MRI showed myositis of the biceps and brachial muscles. Infection was rule out, and direct microscopy showed an extensive muscle infiltration by mononuclear cells and abundant mitosis. Immunohistochemistry was positive for CD3, CD8, Ki 67 (90%), and CD56 compatible with extranodal NK/T cell lymphoma. INTERVENTIONS: The patient initially received immunosuppression treatments (corticoids, cyclofosfamide, and Rituximab) with relapsing episodes. When lymphoma was diagnosed, chemotherapy was started. OUTCOMES: The patient died during chemotherapy. LESSONS: Nasal-type, extranodal NK/T-cell lymphoma should be suspected even when there are no classical findings of neoplasms on histology. Immunohistochemistry is mandatory to rule it out.

A Muscle-Invasive Bladder Cancer Patient With High Tumor Mutational Burden and RB1 Mutation Achieved Bladder Preservation Following Chemotherapy Combined With Immunotherapy: A Case Report.

Neoadjuvant chemotherapy followed by radical cystectomy is the standard of care for patients diagnosed with muscle-invasive bladder cancer (MIBC). However, urinary diversion following radical cystectomy significantly reduces patient quality of life. In addition, patients who significantly respond to neoadjuvant chemotherapy have a strong will to preserve the bladder. Bladder-sparing therapy has become a research focus worldwide. Although the bladder-sparing regimen, referred to as trimodality therapy (TMT), has been accepted, the efficacy of immunotherapy combined with chemotherapy for bladder preservation in patients with MIBC has not yet been published. We describe the case of a 50-year-old male presented intermittent macrohematuria and was diagnosed with bladder urothelial carcinoma by diagnostic transurethral resection of bladder tumor (TURBt) with clinical stage IIIA (cT3bN0M0). A complete response was achieved after four courses of neoadjuvant chemotherapy combined with pembrolizumab. Then, we performed a second TURBt plus randomized biopsy by cystoscopy. The pathology indicated no tumor in the bladder. Adjuvant chemoradiotherapy and immunotherapy were subsequently performed. Imaging examinations, cystoscopy and urine tumor DNA (utDNA) levels were used for surveillance after treatment. Finally, the patient achieved bladder preservation and had remained cancer-free for 19 months at the last follow-up on February 20, 2021. This is the first published case study to describe neoadjuvant chemotherapy plus pembrolizumab followed by concurrent chemoradiotherapy as a novel bladder-sparing regimen and successfully achieved a promising outcome.

Systemic dissemination of tumor cells during transurethral resection in patients with bladder tumor and its clinical relevance: A follow up study.

OBJECTIVE: Tumor cells are shed during transurethral resection of bladder tumor (TURBT) and form the basis for use of single dose immediate chemotherapy instillation to reduce recurrences. Systemic dissemination of these cells along with the irrigation fluid is also possible but not consistently proven. In this study, we evaluated such dissemination of tumor cells into the circulation during TURBT and its clinical impact. METHODS: Patients with primary presentation of bladder tumor who underwent TURBT were included. Peripheral venous blood samples before and after TURBT were analyzed for circulating tumor cells (CTCs) using flow-cytometry. A CD45 negative cell with positive expression of cytokeratin 18, 19, and EpCam was defined as CTC. The CTC counts, pre and post TURBT, were compared and correlated with final histopathology. The patients were also followed up for any local and/or systemic recurrences. RESULTS: Nine (16.98%) out of 53 patients developed a measurable rise in CTCs after TURBT. All of these patients had high grade and muscle invasive disease. Overall, a measurable rise in CTCs was seen in 9 out of 17 (52.94%) patients with muscle invasive disease. There was no difference in the clinico-pathological stage or the status of cystectomy and/or chemotherapy between those who did or did not show a rise in CTCs. On follow up, 7 patients with muscle invasive disease developed local and/or systemic recurrences and the rise in CTCs was not found to be associated with adverse oncological outcomes. CONCLUSIONS: This study confirms the hypothesis of inadvertent dissemination of tumor cells into the circulation during TURBT, especially in patients with high grade and muscle invasive disease. The long-term oncological impact of such dissemination remains to be confirmed.

Renal function outcomes in patients with muscle-invasive bladder cancer treated with neoadjuvant pembrolizumab and radical cystectomy in the PURE-01 study.

The use of pembrolizumab has been largely accepted in several advanced types of cancers. PURE 01 study (NCT02736266) enrolled consecutively 143 patients with muscle-invasive bladder cancer who received 3 cycles of pembrolizumab 200 mg every 3 weeks before planned radical cystectomy (RC). Clinical, pathological and laboratory data were collected to investigate the relationship between renal function, immunotherapy and cancer-related outcomes. Serum creatinine and estimated glomerular filtration rate (eGFR) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-equation 2009 were reported at baseline and after every cycle of pembrolizumab; the T stage from clinical classification TNM (cTNM) was stated before the treatment. Our analysis did not demonstrate a significant impairment of eGFR after any cycle of pembrolizumab, neither in the overall cohort nor in subgroups considering the T stages or the CKD G-categories according to K-DIGO 2012 classification. In conclusion, in neoadjuvant setting before RC our results suggest that pembrolizumab administration is safe for renal function preservation.

The role of neoadjuvant chemotherapy, lymph node dissection, and treatment delay in patients with muscle-invasive bladder cancer undergoing partial cystectomy.

OBJECTIVES: To investigate treatment patterns of partial cystectomy (PC), neoadjuvant chemotherapy (NAC), lymph node dissection (LND), and treatment delays, and the associations with overall survival (OS) among patients with muscle-invasive bladder cancer. PATIENTS AND METHODS: We identified patients with cT2-4cN0cM0 urothelial carcinoma of the bladder in the National Cancer Database who underwent PC from 2007 through 2015. We performed descriptive statistics and assessed temporal trends using the Cochrane-Armitage test. Our outcomes of interest were NAC, LND, and treatment delay defined as ≥8 or ≥12 weeks for patients who underwent NAC or upfront surgery, respectively. We used logistic regression and multivariable Cox proportional hazards models to evaluate predictors and associations with OS, respectively. RESULTS: A total of 9,199 patients met inclusion criteria. Over the study period, PC utilization decreased from 9% to 7% (P = 0.06). Compared with patients who underwent radical cystectomy, patients treated with PC less frequently received NAC (7% vs. 17%, P < 0.01) and LND (57% vs. 91%, P < 0.01), but were less likely to experience treatment delays (25% vs. 31%, P < 0.01). Only 4.1% (27/655) of patients treated with PC received the combination of NAC, LND, and no treatment delay. In a Cox model, adequacy of LND was associated with improved OS (<10 nodes: HR 0.62, 95% CI 0.48-0.81 and ≥10 nodes: HR 0.48, 95% Cl 0.32-0.72). CONCLUSION: PC is uncommon and associated with poorer utilization of NAC and LND, but fewer treatment delays. The adequacy of LND was associated with improved OS while NAC and treatment delay were not.

Neoadjuvant Chemotherapy-Guided Bladder-Sparing Treatment for Muscle-Invasive Bladder Cancer: Results of a Pilot Phase II Study.

PURPOSE: Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy. MATERIALS AND METHODS: Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate. RESULTS: Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory. CONCLUSION: After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

Will virtual multidisciplinary team meetings become the norm for musculoskeletal oncology care following the COVID-19 pandemic? - experience from a tertiary sarcoma centre.

BACKGROUND: Like with all cancers, multidisciplinary team (MDT) meetings are the norm in bone and soft tissue tumour (BST) management too. Problem in attendance of specialists due to geographical location is the one of the key barriers to effective functioning of MDTs. To overcome this problem, virtual MDTs involving videoconferencing or telemedicine have been proposed, but however this has been seldom used and tested. The COVID-19 pandemic forced the implementation of virtual MDTs in the Oxford sarcoma service in order to maintain normal service provision. We conducted a survey among the participants to evaluate its efficacy. METHODS: An online questionnaire comprising of 24 questions organised into 4 sections was circulated among all participants of the MDT after completion of 8 virtual MDTs. Opinions were sought comparing virtual MDTs to the conventional face-to-face MDTs on various aspects. A total of 36 responses were received and were evaluated. RESULTS: 72.8% were satisfied with the depth of discussion in virtual MDTs and 83.3% felt that the decision-making in diagnosis had not changed following the switch from face-to-face MDTs. About 86% reported to have all essential patient data was available to make decisions and 88.9% were satisfied with the time for discussion of patient issues over virtual platform. Three-fourths of the participants were satisfied (36.1% - highly satisfied; 38.9% - moderately satisfied) with virtual MDTs and 55.6% of them were happy to attend MDTs only by the virtual platform in the future. Regarding future, 77.8% of the participants opined that virtual MDTs would be the future of cancer care and an overwhelming majority (91.7%) felt that the present exercise would serve as a precursor to global MDTs involving specialists from abroad in the future. CONCLUSION: Our study shows that the forced switch to virtual MDTs in sarcoma care following the unprecedented COVID-19 pandemic to be a viable and effective alternative to conventional face-to-face MDTs. With effective and efficient software in place, virtual MDTs would also facilitate in forming extended MDTs in seeking opinions on complex cases from specialists abroad and can expand cancer care globally.

Quantitative Musculoskeletal Tumor Imaging.

The role of quantitative magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) techniques continues to grow and evolve in the evaluation of musculoskeletal tumors. In this review we discuss the MRI quantitative techniques of volumetric measurement, chemical shift imaging, diffusion-weighted imaging, elastography, spectroscopy, and dynamic contrast enhancement. We also review quantitative PET techniques in the evaluation of musculoskeletal tumors, as well as virtual surgical planning and three-dimensional printing.

Image-guided Sports Medicine and Musculoskeletal Tumor Interventions: A Patient-Centered Model.

The spectrum of effective musculoskeletal (MSK) interventions is broadening and rapidly evolving. Increasing demands incite a perpetual need to optimize services and interventions by maximizing the diagnostic and therapeutic yield, reducing exposure to ionizing radiation, increasing cost efficiency, as well as identifying and promoting effective procedures to excel in patient satisfaction ratings and outcomes. MSK interventions for the treatment of oncological conditions, and conditions related to sports injury can be performed with different imaging modalities; however, there is usually one optimal image guidance modality for each procedure and individual patient. We describe our patient-centered workflow as a model of care that incorporates state-of-the-art imaging techniques, up-to-date evidence, and value-based practices with the intent of optimizing procedural success and outcomes at a patient-specific level. This model contrasts interventionalist- and imaging modality-centered practices, where procedures are performed based on local preference and selective availability of imaging modality or interventionalists. We discuss rationales, benefits, and limitations of fluoroscopy, ultrasound, computed tomography, and magnetic resonance imaging procedure guidance for a broad range of image-guided MSK interventions to diagnose and treat sports and tumor-related conditions.

French Multidisciplinary Approach for the Treatment of MSK Tumors.

Several interventional treatments have recently been integrated into the therapeutic armamentarium available for the treatment of bone tumors. In some scenarios (e.g., osteoid osteoma), interventional treatments represent the sole and definitive applied treatment. Due to the absence of widely shared protocols and the complex multivariate scenarios underlying the clinical presentation of the remaining bone tumors including metastases, therapeutic strategies derived from a multidisciplinary tumor board are essential to provide effective treatments tailored to each patient. In the present review, we present the multidisciplinary therapeutic strategies commonly adopted for the most frequent bone tumors.

Musculoskeletal interventional oncology: current and future practices.

Management of musculoskeletal (MSK) tumours has traditionally been delivered by surgeons and medical oncologists. However, in recent years, image-guided interventional oncology (IO) has significantly impacted the clinical management of MSK tumours. With the rapid evolution of relevant technologies and the expanding range of clinical indications, it is likely that the impact of IO will significantly grow and further evolve in the near future.In this narrative review, we describe well-established and new interventional technologies that are currently integrating into the IO armamentarium available to radiologists to treat MSK tumours and illustrate new emerging IO indications for treatment.

Skeletal Muscle Metastases from Carcinomas: A Review of the Literature.

* Bones are a common site for metastases; however, muscle metastases recently have been more commonly reported, not only as a result of the multidisciplinary approach in the treatment of these patients but also because of more sensitive imaging modalities such as positron emission tomography-computed tomography (PET-CT) that identify these lesions in early stages.* The most common carcinoma is lung carcinoma, with a hematogenous route of spread mainly to the axial region of the body (the psoas muscle, the gluteal muscles, and the paravertebral muscles). * Clinically, skeletal muscle metastases from carcinomas frequently present as painful palpable masses with or without swelling and are commonly found before diagnosis of the primary carcinoma.* Multiple imaging modalities, including radiographs, CT, magnetic resonance imaging (MRI), and PET-CT, have been used for diagnosis and staging, but tissue sampling is needed for a final diagnosis. The most important differential diagnosis of skeletal muscle metastases is with soft-tissue sarcomas.* Treatment is mainly based on chemotherapy and/or radiation; surgery is performed in cases of symptomatic lesions that fail to respond to nonoperative treatment.

Tumor response and endogenous immune reactivity after administration of HER2 CAR T cells in a child with metastatic rhabdomyosarcoma.

Refractory metastatic rhabdomyosarcoma is largely incurable. Here we analyze the response of a child with refractory bone marrow metastatic rhabdomyosarcoma to autologous HER2 CAR T cells. Three cycles of HER2 CAR T cells given after lymphodepleting chemotherapy induces remission which is consolidated with four more CAR T-cell infusions without lymphodepletion. Longitudinal immune-monitoring reveals remodeling of the T-cell receptor repertoire with immunodominant clones and serum autoantibodies reactive to oncogenic signaling pathway proteins. The disease relapses in the bone marrow at six months off-therapy. A second remission is achieved after one cycle of lymphodepletion and HER2 CAR T cells. Response consolidation with additional CAR T-cell infusions includes pembrolizumab to improve their efficacy. The patient described here is a participant in an ongoing phase I trial (NCT00902044; active, not recruiting), and is 20 months off T-cell infusions with no detectable disease at the time of this report.

Extranasal extranodal NK/T-cell lymphoma associated with systemic lupus erythematosus.

Increased incidence of lymphoproliferative disorders is reported in patients with autoimmune diseases, majority of which have a B-cell phenotype and are pathogenetically associated with the reactivation of Epstein-Barr virus (EBV). However, EBV-associated T/NK-cell lymphoma has hardly been reported. We present the case of a 68-year-old-woman, who had been diagnosed with systemic lupus erythematosus (SLE) 28 years back and was treated with various immunosuppressive agents including steroids, cyclophosphamide, and tacrolimus. She presented with a progressively worsening swelling of the right thigh for the last few months. Radiological examination revealed an intramuscular bulky tumor without any other lesions and the biopsy results led to a diagnosis of extranodal NK/T-cell lymphoma, nasal type (ENKL). Concurrent chemoradiotherapy resulted in a complete response, which has been sustained for more than 2 years without requiring additional therapy. After the initiation of chemotherapy, SLE did not worsen with the administration of low-dose corticosteroids. To the best of our knowledge, this is the first case report of a localized extranasal ENKL developing in a patient with SLE.