Combination Treatment of Intratumoral Vidutolimod, Radiosurgery, Nivolumab, and Ipilimumab for Microsatellite Stable Colorectal Carcinoma With Liver Metastases.

INTRODUCTION: Microsatellite stable metastatic colorectal cancer (MSS mCRC) is largely refractory to immune checkpoint inhibition. We hypothesized that a combination of intratumoral TLR9 agonist, radiosurgery and dual PD-1 and CTLA-4 blockade would induce a local focus of immune stimulation, evoking a systemic immune response. PATIENTS AND METHODS: In this phase I single-institution study, patients with MSS mCRC were treated with a priming dose of s.c vidutolimod, 3 intratumoral injections of vidutolimod and radiosurgery, combined with nivolumab and ipilimumab. Cytokine levels were measured at baseline and at 7 (± 2) weeks. Patients were accrued to 4 consecutive cohorts: (1) Safety run-in without radiosurgery, (2) Radiosurgery prior to intratumoral therapy, (3) Radiosurgery prior to intratumoral therapy with a condensed timeline, and (4) Radiosurgery to extrahepatic lesion following completion of intratumoral therapy. RESULTS: A total of 19 patients were accrued. Median age was 59 years (range 40-71), 68% were male, median number of previous systemic treatments was 3 (range 2-5). None of the patients responded, aside from 1 patient, attributed to high tumor mutational burden. Grade 3 liver toxicity was reported in 0%, 0%, 75%, and 17% in cohorts 1 to 4, respectively. Systemic levels of CXCL10 and IL-10 increased, with a median of 407 versus 78 pg/mL (P = .01), and 66 versus 40 pg/mL (P = .03), respectively. CONCLUSIONS: The combination of intratumoral vidutolimod, radiosurgery, nivolumab and ipilimumab was not found to be efficacious in MSS mCRC with liver metastases. The juxtaposition of liver irradiation and intratumoral vidutolimod injection was associated with high hepatic toxicity.

Pulmonary Computed Tomography Parenchymal and Vascular Features Diagnostic of Postablation Pulmonary Vein Stenosis.

PURPOSE: The purpose of this study was to define the full spectrum of pulmonary computed tomography (CT) changes characteristic of postablation pulmonary vein stenosis (PVS). MATERIALS AND METHODS: We retrospectively reviewed our pulmonary vein isolation database. PVS was graded as follows: grade 1:<50%, grade 2: 50% to 75%, grade 3: 76% to 99%, and grade 4: total occlusion. CT parenchymal and vascular changes were detected and correlated with clinical course and nuclear scans. RESULTS: Of 486 patients who underwent pulmonary vein isolation, 56 patients (11%) were symptomatic, prompting referral to CT evaluation. Grades 1, 2, 3, and 4 PVS were documented in 42, 1, 2, and 11 patients, respectively. Apart from PVS, abnormal CT findings were present only in patients with PVS grades 2 to 4. Pulmonary parenchymal changes (consolidation, "ground glass" opacities, interlobular septal thickening, and volume loss) were found in PVS grades 2 to 4. Pulmonary vascular changes (oligemia, "sluggish flow," and collateral mediastinal vessels) were shown in patients with grades 3 to 4 PVS. Concomitant nuclear scans documented reduced lung perfusion. All findings were located to the lobe drained by the affected vein. Complete resolution of pulmonary findings on follow-up CT scans was demonstrated in 20% of patients. Eleven stents were inserted in 7 patients with PVS grades 2 to 4, none of which demonstrated radiologic or clinical resolution. CONCLUSIONS: A typical CT complex of both parenchymal and vascular findings in the affected lobe is diagnostic of postablation PVS. Lack of clinical and radiologic resolution in most patients, even after stent insertion, further highlights the importance of early recognition of this underdiagnosed condition.

Comparative effectiveness of intensity modulated radiation therapy to 3-dimensional conformal radiation in locally advanced lung cancer: pathological and clinical outcomes.

OBJECTIVE: Intensity-modulated radiotherapy (IMRT) has better normal-tissue sparing compared with 3-dimensional conformal radiation (3DCRT). We sought to assess the impact of radiation technique on pathological and clinical outcomes in locally advanced non-small cell lung cancer (LANSCLC) treated with a trimodality strategy. METHODS: Retrospective review of LANSCLC patients treated from August 2012 to August 2018 at Sheba Medical Center, Israel. The trimodality strategy consisted of concomitant chemoradiation to 60 Gray (Gy) followed by completion surgery. The planning target volume (PTV) was defined by co-registered PET/CT. Here we compare the pathological regression, surgical margin status, local control rates (LC), disease free (DFS) and overall survival (OS) between 3DCRT and IMRT. RESULTS: Our cohort consisted of 74 patients with mean age 62.9 years, male in 51/74 (69%), adenocarcinoma in 46/74 (62.1%), stage 3 in 59/74 (79.7%) and chemotherapy in 72/74 (97.3%). Radiation mean dose: 59.2 Gy (SD ± 3.8). Radiation technique : 3DCRT in 51/74 (68.9%), IMRT in 23/74 (31%). Other variables were similar between groups.Major pathological response (including pathological complete response or less than 10% residual tumor cells) was similar: 32/51 (62.7%) in 3DCRT and 15/23 (65.2%) in IMRT, p=0.83. Pathological complete response (pCR) rates were similar: 17/51 (33.3%) in 3DCRT and 8/23 (34.8%) in IMRT, p=0.9. Surgical margins were negative in 46/51 (90.1%) in 3DCRT vs. 17/19 (89.4%) in IMRT (p=1.0).The 2-year LC rates were 81.6% (95% CI 69-89.4%); DFS 58.3% (95% CI 45.5-69%) and 3-year OS 70% (95% CI57-80%). Comparing radiation techniques, there were no significant differences in LC (p=0.94), DFS (p=0.33) and OS (p=0.72). CONCLUSION: When used to treat LANSCLC in the neoadjuvant setting, both IMRT and 3DCRT produce comparable pathological and clinical outcomes. ADVANCES IN KNOWLEDGE: This study validates the real-world effectiveness of IMRT compared to 3DCRT.

Neo-adjuvant Chemo-Radiation to 60 Gray Followed by Surgery for Locally Advanced Non-Small Cell Lung Cancer Patients: Evaluation of Trimodality Strategy.

BACKGROUND: Neoadjuvant chemo-radiation therapy (CRT) dosages in locally advanced non-small cell lung cancer (NSCLC) were traditionally limited to 45 Gray (Gy). OBJECTIVES: To retrospectively analyze outcomes of patients treated with 60 Gy CRT followed by surgery. METHODS: A retrospective chart review identified patients selected for CRT to 60 Gy followed by surgery between August 2012 and April 2016. Selection for surgery was based on the extent of disease, cardiopulmonary function, and response to treatment. Pathological response after neoadjuvant CRT was scored using the modified tumor regression grading. Local control (LC), disease free survival (DFS), and overall survival (OS) were estimated by the Kaplan-Meier method. RESULTS: Our cohort included 52 patients: 75% (39/52) were stage IIIA. A radiation dose of 60 Gy (range 50-62Gy) was delivered in 82.7%. Surgeries performed included: lobectomy, chest-wall resection, and pneumonectomy in 67.3%, 13.4%, and 19.2%, respectively. At median follow-up of 22.4 months, the 3 year OS was 74% (95% confidence interval [CI] 52-87%), LC was 84% (95%CI 65-93), and DFS 35% (95%CI 14-59). Grade 4-5 postoperative complications were observed in 17.3% of cases and included chest wall necrosis (5.7%), bronco-pleural fistula (7.7%), and death (3.8%). A major pathologic regression with < 10% residual tumor occurred in 68.7% of patients (36/52) and showed a trend to improved OS (P = 0.1). Pneumonectomy cases had statistically worse OS (P = 0.01). CONCLUSIONS: Major pathologic regression was observed 68.7% with 60 Gy neoadjuvant CRT with a trend to improved survival. Pneumonectomy correlated with worse survival.

Long-term Imaging of the Lungs After Sealant Bronchoscopic Lung Volume Reduction.

PURPOSE: The aim of the study was to assess the pulmonary temporal changes after bronchoscopic lung volume reduction (BLVR) using sealants for treatment of emphysema. MATERIALS AND METHODS: We retrospectively assessed all chest computerized tomography (CT) and F-18 fluorodeoxyglucose (FDG) positron emission tomography CT scans of patients treated at our institution with BLVR. RESULTS: Eleven patients were treated with sealants: 4 with biological sealants and 7 with synthetic sealants. The first CT scan after biological sealant treatment showed no abnormalities in 8 lobes and 5 nodules, and 3 consolidations in 7 lobes. All findings resolved within 3 months, except for a nodule that decreased after 2 months and remained stable for 9 years. The first CT scan after utilizing the synthetic sealant showed abnormalities in each treated lobe: 19 nodules/masses (16 cavitary, 3 solid) and 3 consolidations. Follow-up CT scans were available for 16 nodules/masses: 1 resolved, 12 slowly decreased in size, 1 remained unchanged, and 2 grew. Of 3 consolidations 1 resolved and 2 decreased in size. FDG positron emission tomography CT scans performed in 2 patients showed FDG uptake higher than mediastinal background activity in 2 nodules in the same patient. CONCLUSIONS: Pulmonary changes after BLVR are variable. After treatment with biological sealants, most findings resolve within 3 months. In contrast, after synthetic sealants, although the majority regress over time, some show waxing and waning in growth that can mimic malignancy. FDG uptake in some of these lesions is suggestive of chronic inflammation. Radiologists should be aware of the spectrum of these pulmonary changes to avoid misdiagnosis of lung cancer.

Mediastinal Imaging Pitfalls.

Potential pitfalls in the interpretation of diseases involving the mediastinum are seen when imaging with computed tomography and [18F]-fluoro-2-deoxy-d-glucose positron emission tomography. These pitfalls can involve any mediastinal structure, including the mediastinal vessels, heart, lymph nodes, thymus, trachea, esophagus, and fat. Misinterpretation of normal variants or benign conditions as pathology can affect staging and alter treatment. After reading this review, the reader should be able to identify common mediastinal imaging pitfalls and apply ancillary measures to confirm the correct diagnosis and thus reach an accurate diagnosis to facilitate correct patient treatment.

Feasibility of Confocal Laser Microscopy in CT-Guided Needle Biopsy of Pulmonary and Mediastinal Tumors: A Proof-of-Concept Pilot Study.

This report describes the use of confocal laser microscopy (CLM) with CT-guided transthoracic needle biopsy (TTNB) for the diagnosis of heterogeneous large mediastinal and lung tumors. The procedure was performed in five patients diagnosed with a mediastinal mass and five patients diagnosed with a lung mass. CLM was used before CT-guided TTNB. Fluorescein administration allowed for the identification of blood vessels in both locations. Malignant cells were identified in mediastinal masses. Complications included one case of pneumothorax. In large tumors, CLM allows vascularized tissue to be differentiated from necrotic and fibrotic areas before biopsy.

Enfermedad pulmonar relacionada con IgG4 - Tres casos no tratados con resultado benigno / IgG4-Related Lung Disease - Three Untreated Cases with a Benign Outcome

La enfermedad relacionada con IgG4 es una condición fibroinflamatoria en la cual los distintos órganos afectados comparten similitudes patológicas. Recientemente se ha caracterizado clínica y radiológicamente esta enfermedad en órganos torácicos. La mayoría de los casos descritos abogan por un tratamiento precoz con terapia inmunosupresora y observan una respuesta rápida y favorable. Describimos 3 casos de enfermedad pulmonar relacionada con IgG4 que no recibieron tratamiento farmacológico y que tuvieron una respuesta clínica y radiológica favorable o estable durante el seguimiento. La terapia inmunosupresora puede no ser necesaria en algunos casos de enfermedad pulmonar relacionada con IgG4

IgG4-related disease is a fibroinflammatory disease in which the organs involved share similar pathological findings. Chest disease has been recently clinically and radiologically characterized. Most reports advocate prompt immunosuppressive therapy and describe a fast and good response. We report 3 cases of untreated IgG4-related lung disease that on follow-up have been clinically asymptomatic and radiologically stable or improved. In some cases of IgG4-related lung disease immunosuppressive therapy may not be warranted

IgG4-Related Lung Disease - Three Untreated Cases with a Benign Outcome.

IgG4-related disease is a fibroinflammatory disease in which the organs involved share similar pathological findings. Chest disease has been recently clinically and radiologically characterized. Most reports advocate prompt immunosuppressive therapy and describe a fast and good response. We report 3 cases of untreated IgG4-related lung disease that on follow-up have been clinically asymptomatic and radiologically stable or improved. In some cases of IgG4-related lung disease immunosuppressive therapy may not be warranted.

Severe influenza A (H1N1): the course of imaging findings.

BACKGROUND: An outbreak of respiratory illness caused by a novel swine-origin influenza virus (influenza A/H1N1 2009) that began in Mexico was declared a global pandemic by the World Health Organization in June 2009. The pandemic affected many countries, including Israel. OBJECTIVES: To compare the course of chest radiographic and computed tomography findings in patients who survived and those who died following admission to the intensive care unit (ICU) or intubation due to severe laboratory-confirmed swine-origin influenza A/H1N1 2009. METHODS: We retrospectively reviewed the patient records (267 radiographs, 8 CTs) of 22 patients (10 males, 12 females) aged 3.5-66 years (median 34) with confirmed influenza A/ H1N1 2009, admitted to the ICU and/or intubated in five major Israeli medical centers during the period July-November 2009. We recorded demographic, clinical, and imaging findings--including pattern of opacification, extent, laterality, distribution, zone of findings, and presence/absence of nodular opacities--at initial radiography and during the course of disease, and compared the findings of survivors and non-survivors. Statistical significance was calculated using the Wilcoxon (continuous variables) and Fisher exact tests. RESULTS: The most common findings on the initial chest radiography were airspace opacities, which were multifocal in 17 patients (77%) and bilateral in 16 (73%), and located in the lower or lower and middle lung zones in 19 patients (86%). Large airspace nodules with indistinct margins were seen in 8 patients (36%). Twelve patients survived, 10 died. Patients who died had multiple background illnesses and were significantly older than survivors (P = 0.006). Radiologic findings for the two groups were not significantly different. CONCLUSION: Airspace opacities, often with nodular appearance, were the most common findings among patients with severe influenza A/H1N1 2009. The course of radiologic findings was similar in patients with severe influenza A/ H1N1 2009 who survived and those who died.

Enigma of missing teeth in maxillofacial trauma.

PURPOSE: The initial evaluation and treatment of trauma victims should follow a planned approach, as delineated by the Advanced Trauma Life Support protocol, with the main concern securing a patent airway. When trauma has been associated with maxillofacial injury, it can complicate airway management owing to aspirated avulsed teeth or dental prosthetic devices. In such cases, endotracheal intubation can be life-threatening, if the foreign bodies are pushed into the upper respiratory tract. The objective of the present report was to illustrate the diagnostic and management problems related to foreign bodies from the oral cavity lodged in the upper airway after blunt maxillofacial trauma or emergency endotracheal intubation. We also discussed how this could be prevented. PATIENTS AND METHODS: A retrospective study was performed at the Department of Oral and Maxillofacial Surgery, Hadassah Medical Center (Jerusalem, Israel). The records of 1,411 patients admitted for treatment of facial trauma during the past 10 years were reviewed. RESULTS: Of the 1,411 patients, 7 (0.5%) had aspirated foreign bodies that had lodged in the airway because of the trauma or subsequent intubation. CONCLUSIONS: The patient's oral cavity and upper airway must be inspected thoroughly before attempting endotracheal intubation. Any foreign body should be removed from the mouth and throat. This process must be undertaken, despite the stressful and limiting conditions of emergency care.

Breast magnetic resonance imaging characteristics in women with occult primary breast carcinoma.

BACKGROUND: Occult breast cancer without clinically or mammographically detectable breast tumor is an uncommon presentation. OBJECTIVES: To assess the role of breast MRI in women with metastatic carcinoma and an occult primary, and to define the MRI characteristics of the primary breast tumor. METHODS: This retrospective study evaluated 20 women with metastatic carcinoma of unknown origin who underwent breast MRI between 2000 and 2006. Four women were excluded, leaving 16 in the study group. Probability of malignancy was assessed according to BIRADS classification. MRI performance in detecting lesions and evaluating disease extent was assessed, with the gold standard being surgical or biopsy pathology. RESULTS: MRI detected suspicious lesions in 15 patients. Lesion size ranged from 0.4 to 7 cm (median 1.5 cm). MRI detected a single lesion in 6 patients (40%), multifocal disease in 3 (20%), multicentric disease in 4 (27%), and bilateral breast lesions in 2 (13%). In 13 patients MRI depicted the primary breast cancer. Initial treatment was surgical in 9; MRI correctly estimated disease extent in 6 (67%), underestimated disease extent in 1 (11%), and overestimated it in 2 (22%). Four patients had biopsy followed by chemotherapy; one had multicentric disease and one had multifocal disease. MR findings were false positive in two patients and false negative in one. CONCLUSIONS: MRI is sensitive in detecting the primary tumor and beneficial in assessing tumor extent. Small size and multiple foci are common features. We suggest that bilateral breast MRI be part of the evaluation of women with metastatic carcinoma and an occult primary.

Percutaneous image-guided splenic procedures: update on indications, technique, complications, and outcomes.

Percutaneous image-guided splenic procedures are seldom performed due to fear of complications, mainly hemorrhage. Percutaneous splenic invasive procedures are, however, safe, and in most cases, the complication rates are similar to those of other abdominal organs. In most patients, biopsy of a focal splenic lesion establishes the diagnosis. Aspiration and drainage of splenic collections are performed obviating the need for splenectomy. In this review we describe the indications, technique, complications, and outcomes of percutaneous splenic biopsy, aspiration, and drainage.

Prenatal MR diffusion-weighted imaging in a fetus with hemimegalencephaly.

We report a case of hemimegalencephaly diagnosed by prenatal MRI with an emphasis on its appearance on diffusion-weighted images. This case shows that in this condition the enlarged hemisphere may show restricted diffusion on prenatal MRI. In our opinion, this finding may result from a combination of increased cellularity and advanced myelination in the affected hemisphere. Restricted diffusion is an additional valuable indicator in the analysis of the fetal brain.

Image-guided cutting-edge-needle biopsy of peripheral lymph nodes and superficial masses for the diagnosis of lymphoma.

OBJECTIVE: To evaluate the diagnostic efficacy of image-guided cutting-edge-needle biopsy of peripheral lymph nodes and superficial masses for the diagnosis of lymphoma, for which many still advocate open surgical resection. METHODS: A retrospective analysis was performed of the medical records of 114 lymphoma patients who presented with peripheral lymphadenopathy and superficial masses and who underwent diagnostic image-guided biopsy. There were 69 non-Hodgkin lymphoma patients, 38 Hodgkin lymphoma patients, and 7 patients who were evaluated for histologic transformation of CLL or high grade lymphoma. RESULTS: Image-guided needle biopsy was diagnostic in 96/114 (84.2%) patients. The procedure was diagnostic in 59/69 (85.5%) of NHL patients and in 30/38 of Hodgkin disease patients (79%). Diagnoses were achieved for all 7 cases where histologic transformation was suspected. CONCLUSION: Percutaneous image-guided needle biopsy is a safe and reliable procedure with a high diagnostic yield. It can be used as a first step in patients suspected of having lymphoma presenting with enlarged peripheral lymph nodes and superficial masses.

Computed tomographic features of tuboovarian abscess.

OBJECTIVE: To describe the spectrum and frequency of computed tomographic (CT) features in tuboovarian abscess (TOA) in order to increase the utility of computed tomography in diagnosing this condition. STUDY DESIGN: Search of our hospital registry found 22 patients diagnosed with TOA who underwent pelvic tomography between the years 1998 and 2001. A retrospective review of their CT scans was performed, and the CT features of TOA were recorded. Clinical signs and symptoms were also summarized. RESULTS: All 22 patients presented with lower abdominal pain. Additional clinical signs of TOA, such as a palpable abdominal mass (23%), vaginal discharge (27%) and fever (36%), were less common. On tomography the majority of TOAs were unilateral (73%) and multilocular (89%) and had fluid density (95%) and a thick, uniform, enhancing wall (95%). Other common CT findings were thickening of the mesosalpinx (91%) and infiltration into pelvic fat (91%). Less common CT findings included bowel thickening (59%), thickening of the uterosacral ligaments (64%) and pyosalpinx (50%). Ascites, lymphadenopathy, peritoneal involvement and hydronephrosis were uncommon findings on tomography. CONCLUSION: Computed tomography is a useful imaging modality in the diagnosis of TOA, especially in cases that are clinically indeterminate. Recognition of the spectrum of CT findings and their frequency can result in improved CT diagnosis of this disease.