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A burn is one of the most difficult injuries people can face.The primary pathology is coagulation necrosis resulting from tissue damage.Many wound care products have been developed to be used in situations such as the poor general condition of the patient and lack of solid area to be grafted. However, the high costs of these products make their use complicated.In this study, the effect of PEMF on cutaneous wound healing in an animal burn model was evaluated and the dose and duration of the magnetic field should be discussed for this effect to occur. Animals were divided into five groups including eight each (n = 40) (Groups 1, 2, 3, 4, 5).Group 1 was the control group; received no treatment after second-degree burn wound. Group 2 received daily wound care with saline. Group 3 received daily wound care with pomade containing mupirocin. Group 4 received Pulsed Electromagnetic Field signal for 60 min (1.5 m T and 40 Hz for seven days and Group 5 also received PEMF signal for 60 min the same frequency and intensity for14 days. Microscopically, second-degree burn wounds were successfully detected in all rats. Histopathological examination results in no significant difference between groups in neutrophil infiltration. The difference between the groups in vascularization was statistically significant between Group II and Group V (p < 0.001) and between Group I and Group V (p = 0.005) Epithelialization was present in 75% of the rats in Group V, while no epithelialization was observed in any of the other groups. In conclusion, we observed a significant improvement in the stasis zone of the group receiving Pulsed Electromagnetic Field for two weeks.

Interventional radiology is playing an increasingly important role in the local treatment of bone metastases; this treatment is usually done with palliative intent, although in selected patients it can be done with curative intent. Two main groups of techniques are available. The first group, centered on bone consolidation, includes osteoplasty/vertebroplasty, in which polymethyl methacrylate (PMMA) is injected to reinforce the bone and relieve pain, and percutaneous osteosynthesis, in which fractures with nondisplaced or minimally bone fragments are fixed in place with screws. The second group centers on tumor ablation. tumor ablation refers to the destruction of tumor tissue by the instillation of alcohol or by other means. Thermoablation is the preferred technique in musculoskeletal tumors because it allows for greater control of ablation. Thermoablation can be done with radiofrequency, in which the application of a high frequency (450 Hz-600 Hz) alternating wave to the tumor-bone interface achieves high temperatures, resulting in coagulative necrosis. Another thermoablation technique uses microwaves, applying electromagnetic waves in an approximate range of 900 MHz-2450 MHz through an antenna that is placed directly in the core of the tumor, stimulating the movement of molecules to generate heat and thus resulting in coagulative necrosis. Cryoablation destroys tumor tissue by applying extreme cold. A more recent, noninvasive technique, magnetic resonance-guided focused ultrasound surgery (MRgFUS), focuses an ultrasound beam from a transducer placed on the patient's skin on the target lesion, where the waves' mechanical energy is converted into thermal energy (65 °C-85 °C). Treatment should be planned by a multidisciplinary team. Treatment can be done with curative or palliative intent. Once the patient is selected, a preprocedural workup should be done to determine the most appropriate technique based on a series of factors. During the procedure, protective measures must be taken and the patient must be closely monitored. After the procedure, patients must be followed up.

Background Although grading systems have been proposed for chromophobe renal cell carcinoma (ChRCC), including a three-tiered system by Paner et al (Paner GP, Amin MB, Alvarado-Cabrero I, et al. A novel tumor grading scheme for chromophobe renal cell carcinoma: prognostic utility and comparison with Fuhrman nuclear grade. Am J Surg Pathol 2010;34:1233–40), none have gained clinical acceptance, and the World Health Organization (WHO) currently recommends against grading ChRCC. Objective To validate a previously published grading scheme and propose a scheme that includes tumor necrosis. Design, setting, and participants A total of 266 patients who underwent nephrectomy for nonmetastatic ChRCC between 1970 and 2012 were reviewed for ChRCC grade according to the Paner system and coagulative tumor necrosis. Outcome measurements and statistical analysis Associations with cancer-specific survival (CSS) were evaluated using Cox proportional hazard regression models and summarized with hazard ratios (HRs). Results and limitations Twenty-nine patients died from RCC; the median follow-up was 11.0 (interquartile range 7.9–15.9) yr. ChRCC grade according to the Paner system was significantly associated with CSS, including the difference in outcome between grade 1 and 2 tumors. Among patients with grade 2 tumors, the presence of tumor necrosis helped delineate patients with worse CSS. As such, the Paner system was expanded to four tiers separating grade 2 into those with and without tumor necrosis. HRs for associations of the proposed grade 2, 3, and 4 tumors with CSS were 4.63 (p = 0.007), 17.8 (p Conclusions The expansion of a previously reported ChRCC grading system from three to four tiers by the inclusion of tumor necrosis helps further delineate patient outcome and can, therefore, enhance patient counseling following surgery. It also aligns the number of ChRCC grades with the WHO/International Society of Urologic Pathology four-tiered grading systems for clear cell and papillary RCC. Patient summary Chromophobe renal cell carcinoma is the third most common type of renal cancer, and unlike other renal cancers, there is no accepted prognostic grading system. In this study, we found that a grading system that included a pathologic feature of tumor necrosis could better define outcomes for patients with chromophobe renal cell carcinoma.

Purpose Despite modern reperfusion and pharmacologic therapies, myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. Therefore, the development of further therapeutics affecting post-MI recovery poses significant benefits. This review focuses on the post-MI immune response and immunomodulatory therapeutics that could improve the wound-healing response. Methods This narrative review used OVID versions of MEDLINE and EMBASE searching for clinical therapeutics targeting the immune system during MI. Preclinical models and clinical trials were included. Additional studies were sourced from the reference lists of relevant articles and other personal files. Findings After MI, cardiomyocytes are starved of oxygen and undergo cell death via coagulative necrosis. This process activates the immune system and a multifaceted wound-healing response, comprising a number of complex and overlapping phases. Overactivation or persistence of one or more of these phases can have potentially lethal implications. This review describes the immune response post-MI and any adverse events that can occur during these different phases. Second, we describe immunomodulatory therapies that attempt to target these immune cell aberrations by mitigating or diminishing their effects on the wound-healing response. Also discussed are adult stem/progenitor cell therapies, exosomes, and regulatory T cells, and their immunomodulatory effects in the post-MI setting. Implications An updated understanding into the importance of various inflammatory cell phenotypes, coupled with new technologies, may hold promise for a new era of immunomodulatory therapeutics. The implications of such therapies could dramatically improve patients’ quality of life post-MI and reduce the incidence of progressive heart failure.

Objective The purpose of this study was to compare the acute histological effects of MicroPulse transscleral cyclophotocoagulation (MPCPC) using the MicroPulse P3 Device and continuous wave transscleral cyclophotocoagulation (CWCPC) on the ciliary body and adjacent structures in human cadaver eyes. Methods Quadrants of 6 human cadaver eyes from 3 different donors were subjected to traditional CWCPC, slow burn CWCPC, MPCPC, or no treatment (internal control). Sutures were used to differentiate different treatment areas on each eye. Differential inking was applied after treatments to aid in microscopic correlation. All specimens were subject to standard histologic processing. Tissue sections were cut at 4 microns and stained with hematoxylin and eosin according to established protocols. Pathologic evaluation by light microscopy was confirmed by a senior pathologist blinded to treatment groups. Results In all 6 eyes, tissues treated with traditional and low burn CWCPC showed variable coagulative tissue damage to the ciliary body compared with untreated tissues. Minimal histologic changes were identified within the ciliary processes, although variable pigment clumping and streaming were noted within the pigmented ciliary epithelium. In contrast to CWCPC, MPCPC-treated tissues showed only minimal coagulative tissue damage to the ciliary body. Variable pigment clumping and streaming, however, were also noted in the pigmented ciliary epithelium in MPCPC-treated tissues. Conclusions In human cadaver eyes, MPCPC treatment caused less tissue disruption to the ciliary body compared with traditional and low burn CWCPC treatments. MPCPC may be a less destructive and more selective method of cyclophotocoagulation when compared with traditional and low burn CWCPC.

Foci of necrosis are frequently seen in malignant tumours and may be due to a variety of causes. Different types of necrosis are given various names based upon their morphological features and presumed pathogenesis, such as coagulative, liquefactive and fibrinoid necrosis. Here, we propose the term 'granular necrosis' (GN) for a specific form of tumour necrosis characterised by the presence of well-defined necrotic foci being sharply demarcated from adjacent viable tumour. A constant feature is loss of architecture resulting in an amorphous necrotic mass containing granular nuclear and cytoplasmic debris, without an associated neutrophilic infiltrate. There is usually extensive karyorrhexis, which in larger tumours is more prominent at the periphery. These foci are often microscopic but may range up to several millimetres or larger in size. This distinctive form of necrosis has been erroneously given a variety of names in the literature including coagulative necrosis and microscopic necrosis, which on the basis of the aforementioned gross and microscopic findings is inappropriate. It is apparent that this is a specific form of necrosis, hence the descriptive term 'granular necrosis' that differentiates this form of necrosis from other types. The presence of GN is recognised as occurring in a variety of tumour types, being commonly seen in renal cell carcinoma, where it has been shown to have independent prognostic significance. In some epithelial and stromal tumours of the uterus, the presence of GN also has prognostic significance and is a defining feature for the differentiation of uterine leiomyoma and leiomyosarcoma. The pathogenesis of GN is unresolved. It does not show the features of apoptosis and in recent studies has been shown to have some of the molecular changes associated with necroptosis.

Highlights • Takotsubo Syndrome (TTS) is increasingly reported in COVID-19 patients • The pathogenic mechanisms underlying TTS in this particular setting are still unknown • Autopsy findings in fatal cases may contribute to understand the possible role of SARS-CoV-2 in the onset of TTS, COVID-19 can involve several organs and systems, often with indirect and poorly clarified mechanisms. Different presentations of myocardial injury have been reported, with variable degrees of severity, often impacting on the prognosis of COVID-19 patients. The pathogenic mechanisms underlying cardiac damage in SARS-CoV-2 infection are under active investigation. We report the clinical and autopsy findings of a fatal case of Takotsubo Syndrome occurring in an 83-year-old patient with COVID-19 pneumonia. The patient was admitted to Emergency Department with dyspnea, fever and diarrhea. A naso-pharyngeal swab test for SARS-CoV-2 was positive. In the following week his conditions worsened, requiring intubation and deep sedation. While in the ICU, the patient suddenly showed ST segment elevation. Left ventricular angiography showed decreased with hypercontractile ventricular bases and mid-apical ballooning, consistent with diagnosis of Takotsubo syndrome (TTS). Shortly after the patient was pulseless. After extensive resuscitation maneuvers, the patient was declared dead. Autopsy revealed a subepicardial hematoma, in absence of myocardial rupture. On histology, the myocardium showed diffuse edema, multiple foci of contraction band necrosis in both ventricles and occasional coagulative necrosis of single cardiac myocytes. Abundant macrophages CD68+ were detected in the myocardial interstitium. The finding of diffuse contraction band necrosis supports the pathogenic role of increased catecholamine levels; the presence of a significant interstitial inflammatory infiltrate, made up by macrophages, remains of uncertain significance.

Purpose: To investigate effects and heat distribution of radiofrequency ablation (RFA) on vertebral tumors in vitro and in vivo swine experiments and its clinical application. Materials and methods: RFA was performed on the swine spine in vitro and in vivo for 20 min at 90 °C at the electrode tip, and the temperature at the electrode tip and surrounding tissues were recorded. Clinical application of ablation combined with vertebroplasty was subsequently performed in 4 patients with spinal tumors. Results: In the in vitro study, the mean temperature at the front and ventral wall of the spinal canal was 50.8 °C and 43.6 °C, respectively, at 20 mm significantly greater than 37.7 °C and 33.7 ± 1.7 °C, respectively, at 10 mm ablation depth. The coagulative necrosis area was significantly (P

An experimental study was carried out on heat transfer of gas with coagulative particles flowing through a packed granular bed. A logarithmic mean temperature difference (LMTD) method was used to obtain the overall heat transfer coefficient. An empirical formula was used to compare with the experimental results. The results show that the heat quantity released by the concretion of coagulative particles has an improved influence on the heat transfer when the inlet gas temperature of packed bed is above the melting point of the coagulative particles and outlet gas temperature is below the melting point. However, the heat quantity absorbed by the melting of coagulative particles can weaken the heat transfer when both the inlet and outlet gas temperature of the packed bed are above the melting point of coagulative particles. Two modified correlations are proposed to give the Nusselt number.

A 7-year-old male castrated domestic rabbit (Oryctolagus cuniculus) was presented with a several day history of anorexia and adypsia. The rabbit was initially diagnosed with severe dental disease and ileus, but when the patient failed to improve and had decreased urinary output, a more thorough workup, including abdominal ultrasonography, was performed. A colocolic intussusception was discovered. Euthanasia was performed, and a necropsy examination confirmed the imaging findings. Histopathology of the affected portions of colon revealed coagulative necrosis, inflammation, and hemorrhage. An underlying cause was not identified.

COVID-19 is a complex disease with many clinicopathological issues, including respiratory, gastrointestinal, neurological, renal, cutaneous, and coagulative ones; in addition, reactive arthritis has been reported by different authors. Here, we hypothesize that a peripheral microangiopathy involving nerve supply, a viral demyelination, or an immune-mediated irritating antigenic stimulus on synovial sheaths after SARS-CoV-2 infection may all induce a carpal, cubital or tarsal tunnel syndrome of variable entity in genetically predisposed subjects associated with myxoid nerve degeneration.

Objective To investigate the features of small lesions of hepatic alveolar echinococcsis paragonimiasis (AE) on conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) imaging. Methods This retrospective study was approved by the Institutional Review Board, and the requirement for informed consent was waived. US and CEUS features of seventeen lesions histopathologically proven hepatic AE were retrospectively reviewed. Nine patients with seventeen hepatic AE lesions who were admitted to our hospital between January 2008 and June 2015 were enrolled. All hepatic AE lesions were small (≤3 cm). The US and CEUS examinations were performed with a Philips IU22 scanner with a 1–5-MHz convex transducer. After US was completed, the CEUS study was performed. Pulse-inversion harmonic imaging was used for CEUS. A bolus injection of 2.4 mL of a sulfur-hexafluoride-filled microbubble contrast agent (SonoVue) was administered. The features of the lesions by US and CEUS were retrospectively reviewed. Results In total, all lesions were detected by US and CEUS. The mean size of the lesions was 1.8 ± 0.7 cm (range: 1.0–3.0 cm). Five patients (55.6%, 5/9) had a lesion in the right hepatic lobe; two (22.2%, 2/9) had two lesions in the left hepatic lobe; and two patients (22.2%, 2/9) had four lesions in the right lobe. Seven lesions (41.2%, 7/17) were hypoechoic nodules and ten (58.8%, 10/17) were hyperechoic nodules. Nine lesions (52.3%, 9/17) were of mixed echogenicity type. Ten lesions (58.8%, 10/17) had a regular shape. Nine lesions (52.3%, 9/27) had a sharp margin and six (35.3%, 6/17) had indistinct margins. Four lesions (57.1%, 4/7) with hypoechoic nodule had small dotted calcifications, none was found in hyperechoic nodule. Seven nodules (41.2%, 7/17) showed short striated blood-flow signals surrounding the margin, on color Doppler flow imaging. By CEUS, All the lesions were hypoechoic with mixed content (). 12 lesions (70.1%, 12/17) were rim enhanced with irregular piece-like nonenhanced internal areas and showed nonhomogeneous hypo-enhancement during the arterial phase, with mixed echogenicity. The main pathological findings included: (1) (1) coagulative or liquefactive necrosis within the lesion with sporadic distribution of wizened alveolar hydatid cysts; and (2) hyperplasia of granulomatous and fibrous tissue around the lesion. Conclusion Hyperechogenicity, mixed echogenicity type, dotted calcification with hypoechogenicity, sharp margin, rim enhancement and piece-like nonenhanced areas could be seen as the main ultrasonographic features of small lesion of hepatic alveolar echinococcosis.

A male patient with obstructive jaundice was found to have an incidental nodule within the inferior vena cava (IVC), below the level of the renal vein, on abdominal imaging. At the time of the Whipple's procedure for pancreatic adenocarcinoma, the IVC mass measuring 3.4×2.7×2.2 cm was also removed. Histologically, the lesion was well circumscribed, composed focally of spindle-shaped cells with cigar-shaped nuclei reminiscent of smooth muscle and a dominant pervasive, pleomorphic, bizarre giant cell component. Two mitoses per 10 high-power fields were identified in the most mitotically active area of the entire tumor, with the vast majority of the tumor being mitotically inert. Additionally, no evidence of coagulative necrosis was noted. The bizarre giant cells had multi- and polylobated configurations, and several were replete with nuclear pseudoinclusions. Both the spindle cell and pleomorphic components displayed strong immunoreactivity for all smooth muscle markers. This lesion conformed morphologically to a smooth muscle tumor with bizarre nuclei or so-called symplastic/bizarre leiomyoma, as encountered in the uterus. However, current thinking based on location in the IVC and the presence of any mitotic activity with cellular atypia makes this lesion a leiomyosarcoma. Perhaps more pragmatic terminology would be smooth muscle tumor with bizarre nuclei and low malignant potential since the limited number of cases described thus far appear to have a more indolent course.

Cryotherapy or cryoablation involves the freezing of tissues to destroy unwanted tissue or to control bleeding. Endoscopic cryotherapy has been developed for gastrointestinal application by through-the-scope noncontact delivery of compressed carbon dioxide gas or liquid nitrogen (cryospray) or contact balloon cryoablation. The mechanism of cryotherapy ablative effects includes immediate injury as well as coagulation necrosis occurring over several hours and days, unlike heat-based thermal ablation. This article reviews the basis, technique, safety, efficacy, and durability for the use of endoscopic cryotherapy in Barrett's esophagus and esophageal adenocarcinoma.

Background There is increasing interest in the development of vessel substitutes, and many studies are currently focusing on the development of biodegradable scaffolds capable of fostering vascular regeneration. We tested a new biocompatible and biodegradable material with mechanical properties similar to those of blood vessels. Methods The material used comprises a mixture of α,β-poly(N-2-hydroxyethyl)- d,l -aspartamide (PHEA) and polylactic acid (PLA), combined with polycaprolactone (PCL) by means of electrospinning technique. Low-molecular-weight heparin was also linked to the copolymer. A tubular PHEA-PLA/PCL sample was used to create an arteriovenous fistula in a pig model with the use of the external iliac vessels. The flow was assessed by means of Doppler ultrasound examination weekly, and 1 month after the implantation we removed the scaffold for histopathologic evaluation. Results The implants showed a perfect leak-proof seal and adequate elastic tension to blood pressure. About ∼3 weeks after the implantation, Doppler examination revealed thrombosis of the graft, so we proceeded to its removal. Histologic examination showed chronic inflammation, with the presence of foreign body cells and marked neovascularization. The material had been largely absorbed, leaving some isolated spot residues. Conclusions The biocompatibility of PHEA-PLA/PCL and its physical properties make it suitable for the replacement of vessels. In the future, the possibility of functionalizing the material with a variety of molecules, to modulate the inflammatory and coagulative responses, will allow obtaining devices suitable for the replacement of native vessels.

The present study reports a rare case of anaplastic malignant melanoma in a 23-year-old female patient, in the anterior maxilla. On clinical examination, the lesion presented as a 5-cm sessile nodule, with brownish irregular macules on the mucosal surface, painless, with a firm consistency ranging from teeth 14 to 24 with palatal and nasal extension causing facial asymmetry and dental mobility. The computed tomography showed irregular lytic bone reabsorption, without dental involvement. The incisional biopsy followed by microscopic examination suggested primitive neuroectodermal tumor, due to the presence of round blue cells, periodic acid-Schiff (PAS)-positive clear cells, with considerable pleomorphism, atypical mitosis, hemorrhagic areas, and coagulative necrosis. Immunohistochemistry revealed high-grade epithelioid neoplasm and a diagnosis of invasive melanoma was concluded; the melanoma was positive for S-100 protein, gp100, and SOX 10 antigens. The patient underwent partial maxillectomy with no postsurgical complications after 3-month follow-up. The aggressive nature of the lesion and its prognosis are discussed.

We report a rare case of primary pulmonary synovial sarcoma that underwent spontaneous regression after a transbronchial biopsy. A 38-year-old woman with a well-demarcated solitary mass shadow on chest roentgenogram was referred to us. A transbronchial biopsy was performed, and immunohistochemical results as well as detection of SYT-SSX1 (SYnovial sarcoma Translocation-Synovial Sarcoma X chromosome breakpoint) transcripts resulted in a diagnosis of synovial sarcoma. A right lower lobectomy was performed during video-assisted thoracoscopic surgery. Pathologic examination revealed widespread coagulative necrosis with feeding arterioles occluded by organized thrombi. To our knowledge, this is the first report of a case of spontaneous regression of primary pulmonary synovial sarcoma.

The aim of this study was to evaluate anaemia, serum iron concentrations and δ-aminolevulinate dehydratase (ALA-D) activity in laying hens infected naturally by Salmonella Gallinarum and having severe hepatic lesions. Liver and serum samples were collected from 27 laying hens (20 infected and seven uninfected). The δ-ALA-D activity, haematocrit and serum iron concentrations were evaluated. There were significant decreases in δ-ALA-D activity, haematocrit and serum iron concentrations (P

Steam popping frequently occurs during conventional high-power radiofrequency (RF) ablation, increasing the risk of tumor spread. The aim of this study was to evaluate the effect of a low-power RF ablation protocol on the intensity and timing of steam popping in ex vivo bovine liver.High-power (maximum 200 W; group 1) and low-power (maximum 70 W; group 2) RF ablation protocols were established. In the first phase, RF ablation was conducted for 12 min. Ablation volume, intensity, and timing of maximal popping sounds and total energy generated for RF ablation were compared between groups 1 and 2. In the second phase, RF ablation was conducted until maximal popping occurred, and ablation zones on histologic specimens were compared.Relative to group 1, maximal popping occurred at significantly delayed timing in group 2 (50 s ± 11 vs 397 s ± 117; P.001), but without a difference in intensity (ratios vs reference sound of 0.70 ± 0.18 vs 0.83 ± 0.26; P = .138). The ablation volume after 12 min of RF ablation did not differ between groups 1 and 2 (18.46 cm(3) ± 1.35 vs 15.78 cm(3) ± 0.64; P = .086). However, in the histologic specimens obtained when maximal popping occurred, the area of complete coagulative necrosis was significantly larger in group 2 (P.05).Low-power RF ablation delays steam popping while providing comparable therapeutic effects to high-power RF ablation. Delaying maximal popping may prevent tumor cell dispersion because maximal popping occurs after an adequate ablation zone has been achieved.

Although numerous histologic prognostic parameters have been investigated for RCC, those with clinical utility are very limited in number. Tumour morphotype is of prognostic significance. Chromophobe RCC has a more favourable outcome than clear cell and papillary RCC, which in turn is associated with a more favourable outcome than collecting duct RCC. Both clear cell tubulopapillary and tubulocystic RCC appear to have an excellent prognosis. The presence of sarcomatoid or rhabdoid differentiation is a marker of poor prognosis, with sarcomatoid change being associated with median survivals of

Cresol, which is used as a disinfectant and insecticide, has erosive effects on epidermal and epithelial tissues in the body. Oral exposure causes gastrointestinal corrosive injuries as a direct chemical burn. We report herein a case of suicidal poisoning by ingestion of cresol solution. An octogenarian man with depression was found dead approximately 14 h after exposure to less than 500 mL of saponated cresol solution. Macroscopically, corrosive lesions such as red-to-brown-colored epithelium and edematous thickening of walls were seen in the skin, mouth, oral cavity, esophagus, and stomach. Histopathologically, coagulative necrosis and vascular dilatation were detected from mucosal to muscular layers in the esophagus, stomach, and duodenum. Congestive edema of the lungs, edematous changes in the brain, and proximal tubular necrosis of the kidneys were seen, suggesting acute circulatory disturbance due to shock. This human case offers valuable information on the direct irritation and shock induced by systemic exposure to corrosive substances.

Magnetic hyperthermia ablation is a new and minimally invasive modality for localized tumor removal. However, an inadequate ablation dosage can leave a residual tumor or cause a variety of complications. In addition, commonly used magnetic nanoparticles can easily escape from the tumor tissue, which present potential safety problems. In this study, a smart phase transitional and injectable implant based on biocompatible poly lactic-co-glycolic acid (PLGA) implant incorporating magnetic material (Fe powder) and anti-cancer drug (doxorubicin (DOX)) was developed. The magnetic-induced hyperthermia and release efficiency of DOX were evaluated in vitro. Drug release can be controlled under external alternating current magnetic field (AMF). The results of the in vivo tumor therapeutic efficacy showed that when exposed to external AMF, this smart injectable DOX/PLGA-Fe implant could converse magnetic energy into heat and accelerate the release of DOX, which leads to increasing the temperature to achieve tumor coagulative necrosis and accelerating the release of DOX to enhance residual tumor apoptosis. Furthermore, there was no leakage of magnetic material, as demonstrated using real-time ultrasound (US) and computerized tomography (CT) imaging, realizing the guidance and monitoring of tumor therapy. In conclusion, this smart phase transitional and injectable implant DOX/PLGA-Fe has the ability to improve the efficiency of this newly developed minimally invasive magnetic ablation of tumor treatment technique, and will provide a new avenue of developing minimally invasive synergistic tumor therapy.

Salmonella Indiana has emerged in recent years as an important zoonotic pathogen, but its pathogenicity has not been fully elucidated. In this study, using in vivo and in vitro animal and cellular experimental model systems, we evaluated the pathogenicity of Salmonella Indiana (S. Indiana) compared with three other serotypes of Salmonella, S. Enteritidis, S. Typhimurium and S. Thompson. The animal experiments included observations of clinical symptoms, pathological changes and determination of median lethal dose in mice. The adhesion and invasiveness and intracellular proliferative capacity of Salmonella in vitro were measured with the murine macrophage-like cell line RAW264.7 cells and the human colon adenocarcinoma cell line Caco-2 cells. The results of animal experiments showed that S. Indiana, S. Enteritidis, S. Typhimurium and S. Thompson caused histopathological changes in most organs to varying degrees, primarily in the liver and intestine of mice. The gross lesions included white necrotic foci on the liver surface with different levels. The histopathological changes of monocyte/macrophage infiltration and coagulative necrosis were observed in the liver. Intestinal villi became short and were sloughed off, and lymphocyte infiltration was found in the submucosa. Compared with the other serotypes, the pathological changes caused by S. Indiana were slighter and had a relatively high median lethal dose in mice. The results of adhesion and invasion tests showed that the intracellular growth trend of most Salmonella strains was positively correlated with the number of pathogens adhering to and invading cells. Compared with the strains of the other three serotypes, most S. Indiana strains exhibited significantly lower adhesion and invasiveness to RAW264.7 and Caco-2 cells within 30 min. Most S. Indiana strains displayed twice to four times lower intracellular proliferation within 24 h in RAW264.7 cells. In conclusion, S. Indiana was pathogenic, but its pathogenicity was lower than that of S. Typhimurium and S. Enteritidis, and was similar to that of S. Thompson.

The collection and heat transfer characteristics of hot gas with coagulative particles flowing through a novel fixed granular bed with embedded heat exchange tubes are experimentally investigated. The NaCl dust is used as coagulative particles, and the SiO2 dust is used as the solid particles to replace the NaCl for comparison. The experimental results show that the high collection efficiency can be achieved earlier for the coagulative particles than the solid particles, but the corresponding pressure drop is larger. In the initial stage of filtration, the overall heat transfer coefficient is higher for the coagulative particles than the solid particles, which increases with the rise of the inlet particles concentration. However, in the later stage of filtration, the overall heat transfer coefficient is lower for the coagulative particles than the solid particles, which increases while the inlet particles concentration decreases. The pressure drop caused by the coagulative particles increases with the decrease of the gas velocity and the rise of the inlet particles concentration. This novel structure can realize the high collection efficiency of more than 98% and the high waste heat recovery efficiency of more than 70% simultaneously.

Background & Aim Acute kidney injury (AKI) is a life-threatening postoperative complication, affecting 10-30% of treated patients and characterized by the damage to the proximal tubular cells, thereby markedly impairing renal function.1,2,3 15% of patients develop chronic kidney disease (CKD) and fibrosis, eventually managed by hemodialysis and kidney transplantation.4 Mesenchymal stem cells have been shown to possess anti-inflammatory and immunomodulatory properties and be able to aid in tissue repair.5 A link between AKI and CKD has been established and the optimal treatment approach to reduce the high unmet medical need and an economical burden is still being researched.6 Placenta-derived mesenchymal stem cells (PSCs) may be a viable approach to treat AKI and prevent subsequent CKD development. Methods, Results & Conclusion M.: PSCs have been isolated using GMP grade materials, cultivated for three weeks and characterized by yield, viability, flow cytometry and potency in vitro. Wistar rats (8-12 wk) underwent preclinical ischemia-reperfusion injury (IRI). Two experimental groups received treatment. Experimental group (Index) received 3 × 105 of PSCs in the corticomedullar region of each kidney. Control group (Control) received PBS vehicle solution. Survival analysis was carried out till day 7. Urine and blood serum samples were collected on day 0, 3 and 7 and analysed for urine volume/24hrs., protein, creatinine, urea, Na+ and K+. Histological kidney analysis on days 3 and 7 for evaluation of tubular necrosis. R. PSCs had a consistent yield, viability, MSCs markers expression and suppressed proliferation of T cells. Survival rate improved – 100% (Index) vs. 75% (Control). Serum urea and K+ was reduced in index group on day 7 (p Serum creatinine was 1.9 and 1.6 times lower in index group on days 3 and 7, respectively. Na+ was similarly lower after 7 days after PSCs injection. Extensive acute tubular necrosis (ATN) with broad coagulative tubular epithelial necrosis was evident after 3 days in the Control group. Variable extent of ATN without significant coagulative necrosis was observed after 3 and 7 days of Index group. C. Placental derived stem cells have the potential to prevent initial kidney fibrosis cascade through ameliorating initial kidney damage and improving kidney function. A superior 100% survival rate of treated animal group exhibits the potential of characterised PSCs to be used in a larger scale preclinical tumorigenicity and toxicity studies and subsequent clinical first-in-human studies.

Gliomas display a poor disease prognosis causing death within 15 months after diagnosis. Chemotherapy has offered some hope to target this, however, it is majorly ineffective due to the low therapeutic window, poor efficacy and high cytotoxicity. To overcome these challenges, we conjugated Angiopep-2, a cell penetrating peptide (CPP) to Iron Gold (Fe-Au) alloy nanoparticles and investigated the ability of Ang-Fe-Au Nps conjugate to limit glioma growth via magnetic field induced hyperthermia. Our results show that 6.44 nm sized conjugated Fe-Au Nps were superparamagnetic, enhanced negative Glioma image contrast and displayed a 12 °C temperature elevation when magnetically stimulated, indicating applications in medical imaging and hyperthermia-based therapy. Angiopep-2 conjugation resulted in 1.5-fold higher ingestion by C6 glioma cells than L929 fibroblasts, indicating specific glioma targeting and resulting in 90 % decrement in cell viability due to magnetic field induced hyperthermia. Immunohistochemical analysis showed an enhanced coagulative necrosis, glial fibrillary acidic protein (GFAP) expression and decreased Ki67 labelling index in rat treated with Ang-Fe-Au Nps which translated to a 5-fold decrement in tumor volume, consequently resulting in an increased survival time by 7 days. The dual application of this platform opens new doors towards cancer theranostics with minimal invasiveness.

Video Objective Uterine leiomyosarcoma (uLMS) is aggressive mesenchymal neoplasm and is associated with a high risk of recurrence and poor prognosis. The 5year overall survival rate is about 60% even in FIGO stage I disease. There is no firm evidence of chemotherapy, so surgical resection should be considered to control the disease in case of localized recurrence. We will report a case underwent total laparoscopic complete resection for recurrent mass involved sigmoid colon and right ureter. Setting Gynecology and Obstetrics department of a general hospital. Interventions The patient was a 56-year-old woman underwent total laparoscopic hysterectomy with bilateral salpingo-oophorectomy for enlarged 9cm cervical leiomyoma. The pathological examination of the uterus resected showed cytologic atypia,nuclear mitoses and coagulative necrosis, she was diagnosed as primary uLMS, stageⅠB. She rejected to receive adjuvant chemotherapy. After 7months, the isolated metastasis in pelvic and lung was suspected. Magnetic resonance imaging revealed that the 4cm tumor possibly be involved sigmoid colon and right lower ureter. Resection of the recurrent mass with segmental bowel resection and partial resection of ureter with ureteroneocystotomy was performed laparoscopically without any complications. Complete tumor resection with histologic negative margins was achieved. She had postoperative adjuvant chemotherapy with doxorubicinfor 6 cycles and additional surgery for lung meta is scheduled. Also, we experienced another three salvage cases with successful resection in combination with laparoscope and thoracoscope. Conclusion The surgical indications for recurrent uLMS should be selected, but the complete resection of localized recurrence may lead to control the disease. Minimally invasive approach may be one of the feasibleoption.

Background and objectives Currently, extended resection and preoperative neoadjuvant chemotherapy are the two main modalities for improvement of the resection rate and R0 resection rate of borderline resectable pancreatic cancer. The past few years, however, have witnessed some progress in the treatment of unresectable pancreatic cancer with high intensity focused ultrasound (HIFU). The aim of this study is twofold: first, to evaluate the feasibility and safety of HIFU ablation as a preoperative adjuvant therapy for borderline resectable pancreatic cancer, and second, to conduct pathological analyses to verify the safety and effectiveness of HIFU treatment of pancreatic cancer. Methods From January 2011 to December 2012, 30 patients with borderline resectable pancreatic cancer underwent HIFU ablation by Haifu Model-JC200 Focused Ultrasound Tumor Therapeutic System prior to radical surgery. The effect of pre-operative HIFU ablation was evaluated by post-HIFU functional imaging results, operation time of radical surgery, blood loss volume, R0 resection rate, postoperative 1-year survival rate and Ca199 curve. Postoperative pathological specimens were obtained for histological examination. Results All 30 patients with borderline resectable pancreatic cancer had completed the treatments and follow-ups. Functional image assessment after HIFU treatment showed a mean tumor ablation rate of (61.5 ± 24.3)%. 28 patients underwent radical resection of pancreatic cancer 7–9 days after HIFU treatment (23 cases underwent pancreaticoduodenectomy. 4 patients underwent pancreatectomy and 1 patient had total pancreatectomy). 7 patients underwent combined resection and reconstruction of portal-superior mesenteric vein (23.3%), with the resectability rate of 93.3%, the R0 resection rate of 92.7%, and the 1-year survival rate of 96.7%. The biological coagulative necrosis regions identified by the postoperative pathological examination matched well with the necrosis foci identified by post-operative functional imaging. Conclusion The effectiveness of HIFU ablation of pancreatic tumors, as well as interstitial tissues within he main vascular spaces was confirmed by post-operative pathological examinations. Based on these observations, we conclude that preoperative HIFU ablation of borderline resectable pancreatic cancer can significantly improve the resection rate, R0 resection rate, and reduce the difficulty and risk of surgery. Therefore, HIFU may be a valuable pre-operative adjunct therapy for resectable pancreatic cancer. However, the safety and the efficacy on the improvement of the surgery need to established with future multicenter, randomized studies.

Objectives The purpose of this study was to assess the feasibility of pulmonary vein (PV) isolation using low-intensity collimated ultrasound. Background Contemporary approaches to PV isolation are limited by the technical complexity of mapping and ablation. We describe a novel approach to left atrial anatomic rendering and PV isolation that aims to overcome some of these limitations by using low-intensity collimated ultrasound (LICU) system, which allows for near real-time geometry creation and automated ablation in a porcine model. Methods Twenty swine were anesthetized, and the LICU ablation catheter was placed in the left atrium via percutaneous transseptal access. Ultrasound M-mode–based anatomies of the inferior PVs were successfully created, and ablation was performed under automatic robotic control along a user-defined lesion path. One animal was excluded because of device failure. Results All target PVs in the 19 remaining animals were isolated acutely, requiring a mean of 1.6 applications. Ten animals were sacrificed acutely, and the remaining 9 survived for 35 ± 11 days. Of these 9, 1 animal was excluded from analysis because the index lasso position could not be reliably recreated. PVs in 5 of 8 animals remained isolated at sacrifice. Of the 77 total histological sections, 62 lesions (80.5%) were noted to be transmural. Lesions were homogeneous and characterized by coagulative necrosis and fibrous tissue. The mean myocardial thickness was 2.66 ± 1.80 mm, and the mean lesion depth was 4.28 ± 1.97 mm. No extra cardiac or collateral lesions were noted. Conclusions This study demonstrates the safety and efficacy of a novel noncontact ultrasound mapping and ablation system to produce continuous transmural lesions that can isolate PVs in a porcine model.

High-intensity focused ultrasound (HIFU) is a rapidly developing, non-invasive technique for local treatment of solid tumors that produce coagulative tumor necrosis. This study is aimed to investigate the feasibility of proton magnetic resonance spectroscopy (MRS) on early assessing treatment of HIFU ablation in rabbit with VX2 liver tumor. HIFU ablation was performed on normal liver and VX2 tumor in rabbit, and MRS was performed on normal liver and VX2 tumor before and 2 days after 100% HIFU ablation or 80% ablation in tumor volume. Choline (Cho) and choline/lipid (Cho/Lip) ratios between complete and partial HIFU ablation of tumor were compared. Tissues were harvested and sequentially sliced to confirm the necrosis. In normal liver, the Cho value liver was not obviously changed after HIFU (P > .05), but the Cho/Lip ratio was decreased (P < .05). Cho in liver VX2 tumor was much higher than that in normal liver (P < .001). Cho and Cho/Lip ratio were significantly decreased in tumor after complete HIFU ablation and partial HIFU ablation, and the Cho value in complete HIFU tumor ablation did not show any difference from that in normal liver after HIFU (P > .05); however, the Cho value in partial ablation was still higher than that in normal liver before or in tumor after complete HIFU treatment due to the residual part of tumors, and Cho/Lip ratio is lower than that in complete HIFU treatment (P < .001). The changes in MRS parameters were consistent with histopathologic changes of the tumor tissues after treatment. MRS could differentiate the complete tumor necrosis from residual tumor tissue, when combined with magnetic resonance imaging. We conclude that MRS may be applied as an important, non-invasive biomarker for monitoring the thoroughness of HIFU ablation.

This article reviews toxic chemicals that cause irritation and damage to single and multiple organ systems (corrosion) in an acute fashion. An irritant toxic chemical causes reversible damage to skin or other organ system, whereas a corrosive agent produces irreversible damage, namely, visible necrosis into integumentary layers, following application of a substance for up to 4 hours. Corrosive reactions can cause coagulation or liquefaction necrosis. Damaged areas are typified by ulcers, bleeding, bloody scabs, and eventual discoloration caused by blanching of the skin, complete areas of alopecia, and scars. Histopathology should be considered to evaluate questionable lesions.

Ethnopharmacological evidence Antrodia camphorata, a highly valued polypore mushroom native only to Taiwan, has been traditionally used as a medicine for anti-inflammation. Aim of the study In this study, anti-inflammatory effects of Antrodia camphorata (AC) and its active compound, ergostatrien-3β-ol (ST1), were investigated in a mouse skin ischemia model induced by skin flap surgery on the dorsal skin. Materials and methods A U-shaped flap was elevated on the dorsal skin of the nine-week-old male mice. Mice were randomly assigned to six groups for treatment (n=6) including normal skin/propylene glycol (PG), surgical skin flap/PG, solid-state-cultured AC (S/AC), wood-cultured AC (W/AC), high-dose ST1 (H-ST1), low-dose ST1 (L-ST1). Antrodia camphorata was dissolved in 25 μL PG and smeared on the skin flap every six hours for 24 h. At the end of the experiment, each mouse was anesthetized, and skin tissues were collected from their back for histopathological analysis, extracting RNA and protein according to our previous reports. Results Skin-flap-induced ischemia damage significantly increased the expression of the iNOS, COX2, and IL-6 proteins and decreased the expression of IκB protein. In addition, focal, moderate coagulative necrosis with inflammatory cell infiltration was found in the epidermis, and moderate inflammatory cells and necrosis with slight edema was noted in the sub-dermis at 24 h after skin flap surgery. However, treatment with solid-state-cultured or wood-cultured AC, or with its derived ST1 active compound, significantly reduced the necrosis and inflammatory cell infiltration in both the epidermis and sub-dermis of the skin flap. The treatments also reduced the inflammatory response by decreasing the expression of inflammation-related genes including iNOS, IL-6, TNF-α, and NF-κB, as shown by changes in RNA and protein expression, when compared with the surgical skin flap procedure alone. Conclusions These results demonstrated that methanolic extracts of wood-cultured fruiting bodies and solid-state-cultured mycelia from Antrodia camphorata have excellent anti-inflammatory activities and thus have great potential as an addition for hydrocolloid dressings.

Testicular seminoma is a relatively common testicular cancer; however, testicular seminoma with pseudocyst is an extremely rare. The ‘burned-out’ phenomenon in germ cell tumors refers to a germ cell tumor in extra-gonadal tissues with spontaneous regression of an intra-gonadal tumor. We present a case of the testicular seminoma with pseudocyst and coagulation necrosis like burned-out tumor without metastasis.

A 64-year-old woman was found dead in her home. At autopsy, although relatively fresh bruises were found on her body, no lethal injury was observed in an internal observation. Mild edematous swelling of the right half of the medulla oblongata was observed. There was acute medial medullary infarction (MMI), which mainly involved the nucleus hypoglossi, medial lemniscus, hypoglossal root, inferior olivary nucleus, and pyramidal tract. Subacute infarction of the lower part of the cerebellum was also found, and severe atherosclerosis of the right vertebral artery containing thrombi was found as the culprit lesion. Immunohistochemistry using amyloid precursor protein (APP) was positive in neuronal tissue in the nucleus ambiguus, despite not showing coagulative necrosis in the nucleus. Therefore, acute ischemic necrosis of the nucleus ambiguus, which is considered to be a component of the dorsal respiratory group, may be a significant finding for her expected death. Immunohistochemistry of APP may be useful for confirming the precise extent of acute ischemia in brain stem infarction, such as unilateral MMI.

Thermal ablation is a widely used minimally invasive treatment modality for different cancers. However, lack of a real-time imaging system for accurate evaluation of the procedure is one of the reasons of local recurrences. Shear waves elastography (SWE) is a new ultrasound (US) imaging modality to quantify tissue stiffness. The aim of the study was to assess the feasibility and accuracy of US elastography for quantitative monitoring of thermal ablation and to determine the elasticity threshold predictive of coagulation necrosis.A total of 29 in vivo thermal lesions were performed in pig livers with radiofrequency system. SWE and B-mode images were acquired simultaneously. Liver elasticity was quantified by using SWE data and expressed in kilopascal. After the procedure, pathologic analysis of treated tissues was compared with US images. The sensitivity and positive predictive value of the SWE maps of tissue elasticity were calculated and compared with the boundaries of the pale coagulation necrosis areas found at pathology.The liver mean elasticity values before and after thermal therapy were 6.4 ± 0.3 and 38.1 ± 2.5 kPa, respectively (P 0.0001). For a threshold of 20 kPa, sensitivity (i.e., the rate of pixels correctly detected as necrosed tissue) was 0.8, and the positive predictive value (i.e., the rate of pixels in the elastographic map20 kPa that actually developed coagulation necrosis) was 0.83.Tissue areas with coagulation necrosis are significantly stiffer than the surrounding tissue. SWE permits the real-time detection of coagulation necrosis produced by radiofrequency and could potentially be used to monitor US-guided thermal ablation.

Sixteen captive adult horned vipers (Vipera ammodytes ammodytes) were submitted for necropsy examination following a 2-week history of lethargy, anorexia and dyspnoea. Gross lesions included widespread haemorrhage, serosanguineous effusions in the body cavities and multiple pinpoint white to yellow foci in the liver. Microscopically, there was multifocal hepatic coagulative necrosis associated with intranuclear acidophilic inclusion bodies in sinusoidal endothelial cells. Similar endothelial lesions were observed in the myocardium, fat bodies, kidneys and spleen. Transmission electron microscopy revealed numerous virions (100-110 nm) in the nuclei of endothelial cells and intracytoplasmic enveloped virions (140-150 nm) were also found. The gross and histological findings and the ultrastructural features of the intranuclear inclusions and viral particles were consistent with herpesviral infection. To the best of our knowledge, these are the first reported cases of a lethal herpesvirosis in horned vipers and the second report in snakes.

Injuries caused by freshwater stingrays are characterized by intense pain and pathological changes at the lesion site, including oedema, erythema and, in most cases, necrosis. In this study, the systemic myotoxic activity induced by mucus extracts from the dorsal region and stinger of the stingrays Plesiotrygon iwamae and Potamotrygon motoro was described, analysed and quantified. Twenty-four hours after injection of 400 μg of the extracts into the gastrocnemius muscle of mice, the following effects were observed: coagulative necrosis of the muscle tissue, muscle fibre regeneration and the presence of inflammatory infiltrates, including neutrophils, macrophages, and a reduced number of eosinophils and lymphocytes. These changes were also observed, although to a lesser extent, in the gastrocnemius muscles of the contralateral limbs, demonstrating that the extracts from the two species could induce systemic rhabdomyolysis. Based on morphometric analysis, it was observed that the stinger extract of P. motoro was more potent in inducing local and systemic myotoxic activity, followed by the dorsal extract from P. motoro and stinger and dorsal extracts from P. iwamae, which induced similar effects.

Cotyledonoid dissecting leiomyoma was originally described in 1975 in a case report by David et al. as a “grape-like leiomyoma of the uterus”.1 In 1996, Roth et al. coined the name “cotyledonoid dissecting leiomyoma”, based on the tumor's resemblance to cotyledons of the placenta and the accompanying dissecting myometrial component.2 To the best of our knowledge, this is the first case presented of cotyledonoid dissecting leiomyoma (CDL) occurring after a hysterectomy and originating from an extrauterine site. CDL consists of an exophytic component of smooth muscle which is rich in blood supply and has a multinodular gross appearance, suggestive of placental tissue. It typically protrudes from the lateral surface of the uterine cornu into the broad ligament and pelvic cavity. This exophytic component is in continuity with intramural dissecting components, which consist of sinuous processes of neoplastic smooth muscle extending between normal myometrial smooth muscle.2 CDL is a benign process, as histologically there is no nuclear atypia, mitotic activity, or coagulative tumor necrosis, which are suggestive of leiomyosarcoma.4

Video Objective Describing a minimally invasive technique for a solitary intramural myomectomy. Setting A 28-year-old African American nulliparous woman presented with pelvic pressure and ultrasound evidence of a large posterior/fundal intramural fibroid measuring 6 cm. She had abnormal and heavy uterine bleeding that was refractory to medical therapy. Definitive surgical treatment was desired and thus a robotic approach was planned. Interventions Myomectomy of a solitary intramural uterine fibroid is performed robotically. Several surgical tips are utilized and described herein. Tip#1: horizontal incision; Tip#2: Utility of a tenaculum for traction; Tip#3: Electrosurgical coagulative dissection; Tip#4: Layered closure with a resorbable barbed suture. Conclusion Hemostatic horizontal incisions, traction with a tenaculum, coagulative dissection, and the utility of a barbed resorbable suture are all steps one can utilize for successful completion of a myomectomy via robotic route.

Dendritic cell tumors are extremely rare and current knowledge on these tumors is limited. The characteristics of three dendritic cell sarcoma subtypes and their optimal treatment approaches are not fully clarified. We aimed to make a systematic review of the literature and enrich the current data with five new cases. Pooled analysis of 462 reported cases revealed that the tumor had no age, gender or racial predilection. Our analysis suggests that the young age, advanced stage, intraabdominal involvement and unfavorable histological features (i.e. large tumor size, absence of lymphoplasmacytic infiltration, coagulative necrosis, high mitotic count) may predict poor prognosis. Subtypes of this tumor have different clinical behaviors with interdigitating dendritic cell sarcoma being the most aggressive form. In general, surgery is the most effective treatment modality and adjuvant radiotherapy has no significant effect on overall survival of patients. The role of chemotherapy for the management of advanced disease is controversial.

This study aimed to study the clinicopathologic characteristics of epithelioid angiomyolipoma, a variant of angiomyolipoma (AML) in the liver; and to discuss the diagnostic challenges. Five cases of primary liver epithelioid AML were retrieved from our archives from January 2003 to October 2012. The clinicopathologic features of each case were retrospectively reviewed. All 5 patients were female, with age ranging from 36 to 70 years (median, 41 years). The size of the tumor ranged from 1.2 to 25 cm. Histologically, the tumor comprised polygonal cells with granular eosinophilic cytoplasm and accompanied by immunohistochemical expression of HMB-45 ± Melan-A. Variations in growth pattern and cytology were observed. Estrogen receptor was negative in all 5 cases. None showed cytologic atypia, coagulative necrosis, increased mitotic count, or vascular invasion. Epithelioid AML is an uncommon primary liver tumor with a female predominance. The size of the tumor can be variable. This tumor might impose diagnostic difficulty both clinically and histologically. Immunohistochemical staining with melanocytic markers is a promising means to confirm the pathologic diagnosis. A careful assessment of aggressive histologic features is recommended to stratify the risk of aggressive behavior of this tumor.

The aims of this study were to investigate the feasibility of accelerated tissue ablation using a peripheral scanning mode with high-intensity focused ultrasound (HIFU) and to explore the effect of flow rate on total energy consumption of the target tissues. Using a model of isolated porcine liver perfusion via the portal vein and hepatic artery, we conducted a scanning protocol along the periphery of the target tissues using linear-scanned HIFU to carefully adjust the varying focal depth, generator power, scanning velocity and line-by-line interval over the entire ablation range. Porcine livers were divided into four ablation groups: group 1, n = 12, with dual-vessel perfusion; group 2, n = 11, with portal vein perfusion alone; group 3, n = 10, with hepatic artery perfusion alone; and group 4, n = 11, control group with no-flow perfusion. The samples were cut open consecutively at a thickness of 3 mm, and the actual ablation ranges were calculated along the periphery of the target tissues after triphenyl tetrazolium chloride staining. Total energy consumption was calculated as the sum of the energy requirements at various focal depths in each group. On the basis of the pre-supposed scanning protocol, the peripheral region of the target tissue formed a complete coagulation necrosis barrier in each group with varying dose combinations, and the volume of the peripheral necrotic area did not differ significantly among the four groups (p > 0.05). Furthermore, total energy consumption in each group significantly decreased with the corresponding decrease in flow rate (p < 0.01). This study revealed that the complete peripheral necrosis barrier within the target tissues can defined using linear-scanned HIFU in an isolated porcine liver perfusion model. Additionally, the flow rate in the major hepatic vessels may play an important role in the use of the peripheral ablation mode, and this novel mode of ablation may enhance the therapeutic efficacy and tolerability of the treatment of large tumors using HIFU ablation.

Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the GI tract. GISTs form a biological continuum ranging from benign incidentally detected minute lesions (stromal tumourlets) of no clinical significance to large and highly malignant sarcomatous neoplasms. The disease is characterized by indistinct borders between biologically different subsets within its spectrum leading to unpredictable course of the disease in the majority of cases. Availability of effective tyrosine kinase inhibitors underlined the urgent need for a reliable risk assessment system to reliably identify those patients who are at a significant risk for disease relapse and would thus profit from currently available effective targeted molecular therapy. While several risk systems have been established for GIST over the last decade, evidence is growing that no single system is optimal for all patients. Accordingly, an individualized risk system integrating classical parameters (site, size, mitotic index), status of serosal mechanical barrier covering the tumour (presence of tumour rupture or serosal penetration) as well as several other still debatable histological (coagulative necrosis, venous invasion, mucosal infiltration), biomarkers (proliferative index, p16 expression, etc.), and molecular (specific mutation types, adverse chromosomal aberrations, etc.) prognosticators would be of superb value for selecting the most appropriate patient treatment.

Objective To compare the renal ablative capabilities of nonthermal irreversible electroporation (NT-IRE) with those of thermal irreversible electroporation (T-IRE) in a porcine model. Materials and Methods A total of 24 laparoscopic renal ablations were performed in 12 pigs using a novel generator capable of alternately delivering NT-IRE and T-IRE. Each pig underwent unilateral interpolar ablation straddling the renal pelvis and lower pole ablation, using a single modality. The pigs were killed at 24 hours and 7 and 21 days. Basic serum laboratory tests, cardiac enzyme levels, and retrograde pyelograms were obtained before and immediately after ablation and at death. Ablation adequacy and lesion size were assessed by histologic examination. Results All procedures were successfully completed without complications. For NT-IRE vs T-IRE, the median lesion size (long axis) at 24 hours, 7 days and 21 days was 3.0 vs 3.3 cm ( P = 1.0), 2.5 vs 3.9 cm ( P = .04), and 1.2 vs 2.8 cm ( P = .03), respectively. Prolonged urinary extravasation and collecting system scarring were observed only for T-IRE. Both NT-IRE and T-IRE ablated the renal tissue adequately. NT-IRE was characterized by acute hemorrhagic necrosis, sparing the large blood vessels and extracellular matrix, and T-IRE by coagulation necrosis with associated moderate inflammation. Conclusion NT-IRE and T-IRE both safe and effectively ablate normal porcine kidneys. NT-IRE created smaller lesions with unique histologic characteristics. Significant collecting system injury occurred with T-IRE. Additional preclinical evaluation aimed at optimizing the ablation protocols is needed.

Five patients with unifocal, biopsy-proven prostate cancer (PCa) evident on multiparametric magnetic resonance imaging (MRI) were treated with magnetic resonance-guided focused ultrasound (MRgFUS) ablation before radical prostatectomy (RP). An endorectal probe featuring a phased-array focused ultrasound transducer was positioned for lesion ablation under MRI guidance. The tissue temperature and accumulation of thermal damage in the target zone was monitored during the procedure by MRI thermometry. Overlap between the ablation area and the devascularisation of the target lesion was evaluated by contrast-enhanced MRI performed immediately after treatment. The procedure was uneventful, and no adverse events were observed. RP was safely performed without significant surgical difficulties in relation to the previous MRgFUS treatment. The histopathology report showed extensive coagulative necrosis, with no residual tumour in the ablated area. Significant bilateral residual tumour, not evident on pretreatment MRI, was observed outside the treated area in two patients. MRgFUS ablation of focal localised PCa is feasible and, if confirmed in appropriate studies, could represent a valid option for the focal treatment of localised PCa.

High intensity focused ultrasound (HIFU) is emerging as an effective oncology treatment modality according to the clinical experience in the last decade. The temperature at the focus can reach over 65 °C within seconds, denaturing cellular proteins and resulting in coagulative necrosis. HIFU parameters are usually kept the same for each treatment spot in tumor ablation. Because of the thermal diffusion from nearby spots, the lesion size will gradually increase as the HIFU therapy progresses, which leads to insufficient treatment of initial spots and over exposure of later ones. From the viewpoint of the physician, uniform lesions with the least energy exposure and the least energy are preferred in tumor ablation. In this study, an algorithm was developed to determine the number of HIFU pulses delivered to each spot in order to generate uniform lesions that fill the region-of-interest completely. The exposure energies required using different scanning pathways (raster scanning, spiral scanning from the center to the outside, and spiral scanning from the outside to the center), spot spacing (1 mm, 2 mm, 4 mm, and 6 mm) and motion time (from 0 s to 400 s) were compared with each other. It is found that spiral scanning from the outside to the center with spot spacing of 2 mm and motion time less than 10 s needs the least numbers of pulses or HIFU energy in uniform lesion production with the minimal temperature elevation. In addition, the effects of thermal properties of tissue (i.e., specific heat capacity, convective heat transfer coefficient, and thermal conductivity) on HIFU ablation were investigated in order to determine the HIFU treatment planning for various targets. Uniform lesion production in the transparent gel phantom and ex vivo bovine liver samples using the proposed algorithm proved effective and accord with the simulation for different scanning pathways by an extracorporeal clinical HIFU system. Therefore, dynamically adjusting ultrasound exposure energy can improve the efficacy and safety of HIFU ablation, and the treatment planning depends on the scanning protocol and thermal properties of the target.

Thermal plasma is a valued tool in surgery for its coagulative and ablative properties. We suggested through in vitro studies that nonthermal plasma can sterilize tissues, inactive pathogens, promote coagulation, and potentiate wound healing. The present research was undertaken to study acute toxicity in porcine skin tissues. We demonstrate that floating electrode-discharge barrier discharge (FE-DBD) nonthermal plasma is electrically safe to apply to living organisms for short periods. We investigated the effects of FE-DBD plasma on Yorkshire pigs on intact and wounded skin immediately after treatment or 24 h posttreatment. Macroscopic or microscopic histological changes were identified using histological and immunohistochemical techniques. The changes were classified into four groups for intact skin: normal features, minimal changes or congestive changes, epidermal layer damage, and full burn and into three groups for wounded skin: normal, clot or scab, and full burn-like features. Immunohistochemical staining for laminin layer integrity showed compromise over time. A marker for double-stranded DNA breaks, γ-H2AX, increased over plasma-exposure time. These findings identified a threshold for plasma exposure of up to 900 s at low power and