Histology to 3D in vivo MR registration for volumetric evaluation of MRgFUS treatment assessment biomarkers.

Advances in imaging and early cancer detection have increased interest in magnetic resonance (MR) guided focused ultrasound (MRgFUS) technologies for cancer treatment. MRgFUS ablation treatments could reduce surgical risks, preserve organ tissue and function, and improve patient quality of life. However, surgical resection and histological analysis remain the gold standard to assess cancer treatment response. For non-invasive ablation therapies such as MRgFUS, the treatment response must be determined through MR imaging biomarkers. However, current MR biomarkers are inconclusive and have not been rigorously evaluated against histology via accurate registration. Existing registration methods rely on anatomical features to directly register in vivo MR and histology. For MRgFUS applications in anatomies such as liver, kidney, or breast, anatomical features that are not caused by the treatment are often insufficient to drive direct registration. We present a novel MR to histology registration workflow that utilizes intermediate imaging and does not rely on anatomical MR features being visible in histology. The presented workflow yields an overall registration accuracy of 1.00 ± 0.13 mm. The developed registration pipeline is used to evaluate a common MRgFUS treatment assessment biomarker against histology. Evaluating MR biomarkers against histology using this registration pipeline will facilitate validating novel MRgFUS biomarkers to improve treatment assessment without surgical intervention. While the presented registration technique has been evaluated in a MRgFUS ablation treatment model, this technique could be potentially applied in any tissue to evaluate a variety of therapeutic options.

Quantifying the Effect of Topical Nitroglycerin on Random Pattern Flap Perfusion in a Rodent Model: An Application of the ViOptix Intra.Ox for Dynamic Flap Perfusion Assessment and Salvage.

BACKGROUND: Near-infrared spectroscopy can detect changes in tissue oxygenation postoperatively that predict flap necrosis. The authors hypothesized that this technology can be applied along with topical nitroglycerin to measure an improvement in tissue oxygenation that correlates with tissue salvage. METHODS: Dorsal, random pattern flaps measuring 10 × 3 cm were raised using Sprague-Dawley rats. Tissue oxygenation was measured after flap elevation in 10 locations using the ViOptix Intra.Ox. Animals were divided into three groups that received 30 mg of topical nitroglycerin daily, twice-daily, or not at all. Oxygenation measurements were repeated on postoperative day 1 and animals were euthanized on day 7 and evaluated for tissue necrosis. RESULTS: Tissue necrosis was greatest in controls (51.3 mm) compared to daily (28.8 mm) and twice-daily nitroglycerin (18.8 mm; p = 0.035). Three flap perfusion zones were identified: healthy (proximal, 50 mm), necrotic (distal, 20 mm), and watershed. Immediate postoperative tissue oxygenation was highest in healthy tissue (57.2 percent) and decreased to 33.0 and 19.3 percent in the watershed and necrotic zones, respectively (p < 0.001). One day after treatment with nitroglycerin, oxygenation in the healthy zone did not increase significantly (mean difference, -1.5 percent). The watershed (17.8 percent; p < 0.001) and necrotic zones (16.3 percent; p <0.001) did exhibit significant improvements that were greater than those measured in control tissues (7.9 percent; both p < 0.001). CONCLUSIONS: Serial perfusion assessment using the ViOptix Intra.Ox measured a significant improvement in flap oxygenation after treatment with topical nitroglycerin. Within the watershed area of the flap, this increase in tissue oxygenation was associated with the salvage of ischemic tissue.

Optimal treatment strategies for hepatic portal venous gas: A retrospective assessment.

BACKGROUND: Hepatic portal venous gas (HPVG) generally indicates poor prognoses in patients with serious intestinal damage. Although surgical removal of the damaged portion is effective, some patients can recover with conservative treatments. AIM: To establish an optimal treatment strategy for HPVG, we attempted to generate computed tomography (CT)-based criteria for determining surgical indication, and explored reliable prognostic factors in non-surgical cases. METHODS: Thirty-four cases of HPVG (patients aged 34-99 years) were included. Necessity for surgery had been determined mainly by CT findings (i.e. free-air, embolism, lack of contrast enhancement of the intestinal wall, and intestinal pneumatosis). The clinical data, including treatment outcomes, were analyzed separately for the surgical cases and non-surgical cases. RESULTS: Laparotomy was performed in eight cases (surgical cases). Seven patients (87.5%) survived but one (12.5%) died. In each case, severe intestinal damage was confirmed during surgery, and the necrotic portion, if present, was removed. Non-occlusive mesenteric ischemia was the most common cause (n = 4). Twenty-six cases were treated conservatively (non-surgical cases). Surgical treatments had been required for twelve but were abandoned because of the patients' poor general conditions. Surprisingly, however, three (25%) of the twelve inoperable patients survived. The remaining 14 of the 26 cases were diagnosed originally as being sufficiently cured by conservative treatments, and only one patient (7%) died. Comparative analyses of the fatal (n = 10) and recovery (n = 16) cases revealed that ascites, peritoneal irritation signs, and shock were significantly more frequent in the fatal cases. The mortality was 90% if two or all of these three clinical findings were detected. CONCLUSION: HPVG related to intestinal necrosis requires surgery, and our CT-based criteria are probably useful to determine the surgical indication. In non-surgical cases, ascites, peritoneal irritation signs and shock were closely associated with poor prognoses, and are applicable as predictors of patients' prognoses.

The assessment of serum-mediated phagocytosis of necrotic material by polymorphonuclear leukocytes to diagnose and predict the clinical features of systemic lupus erythematosus: an observational longitudinal study.

BACKGROUND: Serum-mediated phagocytosis of antibody- and complement-opsonized necrotic cell material (NCM) by polymorphonuclear leukocytes can be quantified by using a flow cytometry-based assay. The phagocytosis of necrotic cell material (PNC) assay parallels the well-known lupus erythematosus cell test. In this study, we aimed to investigate the diagnostic accuracy of the assay and the relationship with clinical manifestations and disease activity in systemic lupus erythematosus (SLE). METHODS: The diagnostic accuracy for SLE diagnosis of the PNC assay was studied by cross-sectional assessment of blood samples from 148 healthy control subjects and a multicenter rheumatic group (MRG) of 529 patients with different rheumatic symptoms. A cohort of 69 patients with an established SLE diagnosis (SLE cohort) underwent longitudinal clinical and laboratory follow-up for analysis of the temporal relationships between PNC positivity and specific clinical manifestations. RESULTS: In 35 of 529 MRG patients, 13 of whom had SLE, the PNC assay result was positive. Combined positivity of the PNC assay and anti-double-stranded DNA antibodies increased specificity and positive predictive value for SLE diagnosis to 0.99 and 0.67, respectively. In the longitudinal study, 42 of 69 SLE cohort patients had positive results in the PNC assay at least once. PNC assay positivity was associated with current hematological manifestations and could predict mucocutaneous manifestations. When combined with hypocomplementemia, PNC positivity preceded increased Systemic Lupus Erythematosus Disease Activity Index 2000 score, glomerulonephritis, and alopecia. CONCLUSIONS: Serum-mediated PNC by polymorphonuclear leukocytes is commonly but not exclusively seen in patients with SLE. The PNC assay may be used in follow-up of patients with SLE and, especially in combination with other routinely assessed laboratory tests, may help to predict flares and different clinical manifestations, including glomerulonephritis. Our results encourage further development of the PNC assay as a complementary laboratory tool in management of patients with SLE.

Assessment of Fibula Flap Skin Perfusion in Patients Undergoing Oromandibular Reconstruction: Comparison of Clinical Findings, Fluorescein, and Indocyanine Green Angiography.

IMPORTANCE: Complications of partial flap necrosis contribute substantially to morbidity in patients who undergo head and neck reconstructive surgery. OBJECTIVE: To assess the usefulness of clinical findings, intraoperative fluorescein angiography, and intraoperative indocyanine green angiography (ICGA) for evaluation of flap skin paddle perfusion in patients undergoing oromandibular reconstruction who are at high risk of partial skin paddle necrosis. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review from May 21, 1996, to May 27, 2015, at a tertiary care academic medical center. Participants were 73 patients who underwent reconstruction of through-and-through defects of the mucosa, mandible, and skin using fibula free flaps that contained large bilobed skin paddles. MAIN OUTCOMES AND MEASURES: The rates of partial skin paddle necrosis and revision reconstructive surgery. RESULTS: The rates of partial flap necrosis were 8% (n = 2) among 25 patients in whom the skin paddle was trimmed based on ICGA and 33% (n = 16) among 48 patients in whom the skin paddle was trimmed according to clinical findings (P = .02). The rates of revision reconstructive surgery were 20% (5 of 25) when flap skin paddles were trimmed using ICGA and 42% (20 of 48) when trimmed per clinical findings (P = .06). CONCLUSIONS AND RELEVANCE: The use of ICGA may reduce the risk of partial skin flap necrosis in free flaps used in patients undergoing head and neck reconstruction who are at high risk of developing flap necrosis. Indocyanine green angiography imaging should be considered in any flap in which skin paddle viability is uncertain based on clinical findings and in patients in whom the skin paddle extends beyond the primary and adjacent angiosomes. LEVEL OF EVIDENCE: 3.

Radiation necrosis presenting as pseudoprogression (PsP) during alectinib treatment of previously radiated brain metastases in ALK-positive NSCLC: Implications for disease assessment and management.

OBJECTIVES: Radiation necrosis presenting as pseudoprogression (PsP) is relatively common after radiation and temozolomide (TMZ) treatment in glioblastoma multiforme (GBM), especially among patients with GBM that harbors intrinsic increased responsiveness to TMZ (methylated O6-methylguanine-DNA methyltransferase [MGMT] promoter). Alectinib is a second generation ALK inhibitor that has significant CNS activity against brain metastases in anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: We report 2 ALK+ NSCLC patients who met RECIST criteria for progressive disease by central radiologic review due to increased in size from increased contrast enhancement in previously stereotactically radiated brain metastases with ongoing extra-cranial response to alectinib. In both patients alectinib was started within 4 months of completing stereotactic radiosurgery (SRS). The enlarging lesions in both patients were resected and found to have undergone extensive necrosis with no residual tumor pathologically. PsP was incorrectly classified as progressive disease even by central independent imaging review. CONCLUSIONS: Treatment-related necrosis of previously SRS-treated brain metastasis during alectinib treatment can present as PsP. It may be impossible to distinguish PsP from true disease progression without a pathologic examination from resected sample. High degree of clinical suspicion, close monitoring and more sensitive imaging modalities may be needed to distinguish PsP versus progression in radiated brain lesions during alectinib treatment especially if there is no progression extra-cranially.

[Non-invasive assessment of fatty liver]. / A májelzsírosodás nem invazív jellemzésének lehetoségei.

As the result of various harmful effects (infectious agents, metabolic diseases, unhealthy diet, obesity, toxic agents, autoimmune processes) hepatic damage may develop, which can progress towards liver steatosis, and fibrosis as well. The most common etiological factors of liver damages are hepatitis B and C infection, alcohol consumption and non-alcoholic fatty liver disease. Liver biopsy is considered as the gold standard for the diagnosis of chronic liver diseases. Due to the dangers and complications of liver biopsy, studies are focused on non-invasive markers and radiological imaging for liver steatosis, progression of fatty liver, activity of the necroinflammation and the severity of the fibrosis. Authors review the possibilities of non-invasive assessment of liver steatosis. The statistical features of the probes (positive, negative predictive values, sensitivity, specificity) are reviewed. The role of radiological imaging is also discussed. Although the non-invasive methods discussed in this article are useful to assess liver steatosis, further studies are needed to validate to follow progression of the diseases and to control therapeutic response.

Necrotizing pneumonia in children.

AIM: Clinical features and outcome of 36 patients with necrotizing pneumonia (NP) as well as 36 children with parapneumonic effusions (PPE) and 36 with severe control pneumonia (CP) were investigated. The mean age of the patients in the NP, PPE and CP groups were similar (3.8 +/- 3.3 (mean +/- SD), 4.2 +/- 3.0 and 4.2 +/- 3.0 y, respectively (p > 0.05)). The duration of symptoms at presentation were 11.9 +/- 8.5, 9.2 +/- 7.2 and 6 +/- 3.6 d, respectively (p < 0.01). The diagnosis of NP was established by computerized tomography. The mean (mean +/- SD) laboratory results in patients with NP revealed a white blood cell (WBC) count of 19,300 +/- 8700/mm3, erythrocyte sedimentation rate (ESR) of 71 +/- 22 mm/h, C-reactive protein (CRP) of 13.6 +/- 11.7 mg/dl and aspartate aminotransferase (AST) of 66 +/- 132 U/L. The values of WBC, ESR, CRP and AST in the NP group were significantly higher than those of the other groups (p < 0.001). The duration of hospitalization in the NP, PPE and CP groups was 26 +/- 9, 16 +/- 6 and 10 +/- 5 d, respectively (p < 0.001). The number of febrile days was 8 +/- 4, 4 +/- 3 and 3 +/- 3 (p < 0.001), and the duration of normalization of CRP was 14 +/- 4, 11 +/- 4 and 7 +/- 3 d (p < 0.001), respectively. The average cost of treatment was 3476 US dollars, 1646 US dollars and 844 US dollars, respectively (p < 0.001). CONCLUSION: All NP patients except two (94%) were complicated with PPE. The effusion in patients with NP and PPE was complicated with bronchopleural fistula (55% and 0%, respectively, p < 0.001). Surgical treatment was required in 66%, 8% and 0% in patients with NP, PPE and CP, respectively (p < 0.001). The mortality rate was 5.5%, 2.7% and 0% (p > 0.05).

[Fournier's syndrome: diagnostic and therapeutic assessment]. / La sindrome di Fournier: inquadramento diagnostico e terapeutico.

Fournier's syndrome is a disorder involving perineum and scrotum caused by invasive anorectal infection. Aerobic and anaerobic bacteraemia can lead to septic toxicity. Hence the importance of the multidisciplinary treatment and urgent surgical procedures including drainage and necrotic tissue removal is stressed. A case of Fournier's syndrome is reported.