Interstitial Spread Research Articles

Growth patterns of pulmonary metastases: should we adjust resection techniques to primary histology and size?

Safety margins in pulmonary metastasectomy are not yet well defined. We hypothesize that histological subtype, size of the lesion and local growth characteristics must be taken into consideration during metastasectomy. This study was conducted to examine and classify growth patterns at resection margins and define the relationships between aggressive local growth, metastasis size and local recurrence to direct metastasectomy. Histologic sections of pulmonary metastases were prospectively collected and haematoxylin-eosin stains were systematically evaluated and classified by their pattern of lung tissue infiltration. Logistic regression was used to model the association between the subgroups of colorectal, renal cell and epithelial cancers and melanomas and sarcomas. From 183 patients, 412 lung specimens were removed, which contained 459 pulmonary metastases. We found that 58% of all lesions had microscopic signs of aggressive local dissemination. The metastases showed histology-specific patterns of local growth: sarcoma was associated with pleural infiltration; colorectal metastases with interstitial spread and aerogenous spread of floating cancer cell clusters; and melanoma with perivascular growth and with lymph vessel involvement. Aggressive patterns of growth had an increasing probability of around 3% for each additional millimetre of metastasis diameter. Local intrapulmonary recurrence was significantly more common in association with interstitial growth and pleural penetration as well as safety margins <7 mm. Approximately 40% of all lung metastases have a smooth surface and might be resected with small margins. Growth characteristics within the lung differ with the histologic subtype and safety margins should generally increase with the size of the metastasis.

Drain Site Hernia in Adult - Case Report and Review of Literature

Hernia is a very common surgical problem.Drain site hernias are very rare (0.1-3.4 %) incidence quoted in literature. We report the case of a 40year old male who presented with a swelling in the right lower abdomen.CT scan revealed herniation of small bowel with interstitial spread through a former drain site placed after a previous laparotomy 10 years back.

Intramyocardial injection of hydrogel with high interstitial spread does not impact action potential propagation

Injectable biomaterials have been evaluated as potential new therapies for myocardial infarction (MI) and heart failure. These materials have improved left ventricular (LV) geometry and ejection fraction, yet there remain concerns that biomaterial injection may create a substrate for arrhythmia. Since studies of this risk are lacking, we utilized optical mapping to assess the effects of biomaterial injection and interstitial spread on cardiac electrophysiology. Healthy and infarcted rat hearts were injected with a model poly(ethylene glycol) hydrogel with varying degrees of interstitial spread. Activation maps demonstrated delayed propagation of action potentials across the LV epicardium in the hydrogel-injected group when compared to saline and no-injection groups. However, the degree of the electrophysiological changes depended on the spread characteristics of the hydrogel, such that hearts injected with highly spread hydrogels showed no conduction abnormalities. Conversely, the results of this study indicate that injection of a hydrogel exhibiting minimal interstitial spread may create a substrate for arrhythmia shortly after injection by causing LV activation delays and reducing gap junction density at the site of injection. Thus, this work establishes site of delivery and interstitial spread characteristics as important factors in the future design and use of biomaterial therapies for MI treatment. Statement of SignificanceBiomaterials for treating myocardial infarction have become an increasingly popular area of research. Within the past few years, this work has transitioned to some large animals models, and Phase I & II clinical trials. While these materials have preserved/improved cardiac function the effect of these materials on arrhythmogenesis, which is of considerable concern when injecting anything into the heart, has yet to be understood. Our manuscript is therefore a first of its kind in that it directly examines the potential of an injectable material to create a substrate for arrhythmias. This work suggests that site of delivery and distribution in the tissue are important criteria in the design and development of future biomaterial therapies for myocardial infarction treatment.

Extravasation into brain and subsequent spread beyond the ischemic core of a magnetic resonance contrast agent following a step-down infusion protocol in acute cerebral ischemia.

BackgroundLimiting expansion of the ischemic core lesion by reinstating blood flow and protecting the penumbral cells is a priority in acute stroke treatment. However, at present, methods are not available for effective drug delivery to the ischemic penumbra. To address these issues this study compared the extravasation and subsequent interstitial spread of a magnetic resonance contrast agent (MRCA) beyond the ischemic core into the surrounding brain in a rat model of ischemia-reperfusion for bolus injection and step-down infusion (SDI) protocols.MethodsMale Wistar rats underwent middle cerebral artery (MCA) occlusion for 3 h followed by reperfusion. Perfusion-diffusion mismatched regions indicating the extent of spread were identified by measuring cerebral blood flow (CBF) deficits by arterial spin-labeled magnetic resonance imaging and the extent of the ischemic core by mapping the apparent diffusion coefficient (ADC) of water with diffusion-weighted imaging. Vascular injury was assessed via MRCA, gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) penetration, by Look-Locker T1-weighted MR imaging after either a bolus injection (n = 8) or SDI (n = 6). Spatial and temporal expansion of the MRCA front during a 25 min imaging period was measured from images obtained at 2.5 min intervals.ResultsThe mean ADC lesion was 20 ± 7% of the hemispheric area whereas the CBF deficit area was 60 ± 16%, with the difference between the areas suggesting the possible presence of a penumbra. The bolus injection led to MRCA enhancement with an area that initially spread into the ischemic core and then diminished over time. The SDI produced a gradual increase in the area of MRCA enhancement that slowly enlarged to occupy the core, eventually expanded beyond it into the surrounding tissue and then plateaued. The integrated area from SDI extravasation was significantly larger than that for the bolus (p = 0.03). The total number of pixels covered by the SDI at its maximum was significantly larger than the pixels covered by bolus maximum (p = 0.05).ConclusionsThese results demonstrate that the SDI protocol resulted in a spread of the MRCA beyond the ischemic core. Whether plasma-borne acute stroke therapeutics can be delivered to the ischemic penumbra in a similar way needs to be investigated.

Chronic Follicular Bronchiolitis Requires Antigen-Specific Regulatory T Cell Control To Prevent Fatal Disease Progression

To study regulatory T (Treg) cell control of chronic autoimmunity in a lymphoreplete host, we created and characterized a new model of autoimmune lung inflammation that targets the medium and small airways. We generated transgenic mice that express a chimeric membrane protein consisting of hen egg lysozyme and a hemoglobin epitope tag under the control of the Clara cell secretory protein promoter, which largely limited transgene expression to the respiratory bronchioles. When Clara cell secretory protein-membrane hen egg lysozyme/hemoglobin transgenic mice were crossed to N3.L2 TCR transgenic mice that recognize the hemoglobin epitope, the bigenic progeny developed dense, pseudo-follicular lymphocytic peribronchiolar infiltrates that resembled the histological pattern of follicular bronchiolitis. Aggregates of activated IFN-γ- and IL-17A-secreting CD4(+) T cells as well as B cells surrounded the airways. Lung pathology was similar in Ifng(-/-) and Il17a(-/-) mice, indicating that either cytokine is sufficient to establish chronic disease. A large number of Ag-specific Treg cells accumulated in the lesions, and Treg cell depletion in the affected mice led to an interstitial spread of the disease that ultimately proved fatal. Thus, Treg cells act to restrain autoimmune responses, resulting in an organized and controlled chronic pathological process rather than a progressive disease.

Metastasizing Ameloblastoma With Localized Interstitial Spread in the Lung

Ameloblastoma is a locally aggressive, epithelial odontogenic tumor involving mandibles and maxillas. Distant metastasis is a very rare condition and is designated as metastasizing (malignant) ameloblastoma despite its benign histological appearance. Up to now, only 27 well-documented cases of metastasizing ameloblastomas are reported in the literature, and lung is the most commonly involved organ. In previous reports of pulmonary metastasizing ameloblastomas, there was little description of the histopathologic finding. Here, the authors report 2 cases of pulmonary metastasizing ameloblastomas with special emphasis on their interesting, interstitial spread along alveolar septa, resulting in a unique 2-cell pattern under microscopic examination. Pulmonary metastasizing ameloblastoma may pose difficulty in diagnosis if the pathologist is not aware of patient's clinical history of ameloblastoma.

Drain Site Hernia in an Adult: A Case Report

Surgical drains, as useful as they are, have been noted not to be without complications. Small bowel herniation through a previous drain site is a rare complication of abdominal drain insertion. To report a case of strangulated hernia through a drain site. A 46-year-old civil servant was referred to our hospital from a general hospital with a two-week history of progressive abdominal pain and bulge in the right lower quadrant. She was evaluated clinically as with an ultrasonography. Results of tests indicated a laparatomy. She had a previous abdominal drain insertion when she had an emergency exploratory laparatomy for perforated typhoid enteritis in the same hospital 20 years prior to presentation. Exploratory laparatomy done revealed gangrenous loops of small bowel that herniated through a previous drain site with interstitial spread. Resection and end-to-end anastomosis was effected and internal end was closed with non absorbable suture (Nylon 1). Careful insertion and management of surgical drains are necessary so as to prevent hernia complications.

Growth patterns of lung metastases from sarcomas

Complete resection of pulmonary metastases from sarcomas is an established method of treatment. While resection margins are well described for primary sarcoma lesions, minimal knowledge is available about margins and factors influencing local tumour control in the lung. The objective of the present study was to describe intrapulmonary patterns of growth for sarcoma metastases as a basis for planning resections. From January 2006 to January 2009, we retrospectively analysed 261 resected pulmonary sarcoma metastases from 52 patients. All metastases were reviewed for histological characteristics and resection margins. Metastases characterised by a solid, well-defined tumour mass were found in 127 of 261 metastases (48.7%). Interstitial spread (39.8%), vascular infiltration (20.7%), satellite nodules (16.1%) and lymphangitic spread (10.7%) were identified as aggressive histological growth characteristics. Forty-five of 52 patients (86.5%) had metastases with a mitotic index of 10 or more per 10 HPF, underlining their high-grade malignant potential. The following characteristics of aggressive intrapulmonary growth were highly correlated with each other: interstitial growth and lymphangitic spread (p = 0.002), interstitial growth and vascular infiltration (p < 0.001), vascular infiltration and satellite nodules (p = 0.009), interstitial growth and pleural invasion (p = 0.004); by contrast, the presence of a fibrous pseudocapsule (17.2%) was not associated with aggressive growth patterns. Almost half of all pulmonary sarcoma metastases could be identified with aggressive patterns of local growth, and only 17.2% are surrounded by a pseudocapsule which might allow safe resection margins.

Safety distance in the resection of colorectal lung metastases: A prospective evaluation of satellite tumor cells with immunohistochemistry

After complete pulmonary metastasectomy of colorectal lung metastases, tumor recurrence at the site of former resection develops in some patients. Well-described risk factors for local recurrence in the lung include incomplete resection and aerogenous spread of floating cancer cell clusters. The aim of this study was to describe the distribution and frequency of satellite cancer cells or clusters in resected tissue to deduce recommendations for safety margins in the future. Seventeen colorectal metastases from 10 patients were processed. Evaluation for pattern of growth, satellite cancer cells, and inflammatory reaction at the surface of the metastases was performed on 102 sections with CDX2 and cytokeratin 20 stains. The distance between the surface of the nodule and the satellite cancer cell was measured for each satellite and statistically evaluated. As a pattern of growth, interstitial spread, inflammatory reaction, and lymphangitic spread were observed in 41.2%, 35.3%, and 23.5%, respectively. A total of 205 satellite cancer cells were identified in 16 of 17 metastases with a mean distance to the nodule of 0.99 ± 0.85 mm (range, 0.06-6.43 mm). The percentages of satellite tumor cells that are likely to be found within 1.59 mm, 3.43 mm, and 7.4 mm around the nodule are 68.27%, 95.5%, and 99.73%, respectively. Satellite tumor cells, a potential source for local recurrence, are found in a high number around colorectal lung metastases. As a standard of care, a safety distance of 3 mm for small metastases and 8 to 10 mm for larger metastases must be maintained around the lesion to prevent local recurrence.

Pulmonary Lymphangitic Carcinomatosis (PLC): Spectrum of FDG-PET Findings

The lungs are among the most common sites for metastases from a multitude of cancers. The majority of pulmonary metastases appear nodular on radiologic images. Interstitial spread of tumor through pulmonary lymphatics, also known as pulmonary lymphangitic carcinomatosis (PLC), is not uncommon and constitutes approximately 7% of pulmonary metastases. PLC is most often seen with adenocarcinoma of a variety of histologies such as thyroid carcinoma, and melanoma. It is usually noted in late stages of malignancy and therefore is indicative of a poor prognosis. Diagnosis of PLC is usually based on a combination of clinical and radiologic findings. However, the diagnosis is difficult when patients have limited clinical findings or have a history of or the possibility of other interstitial lung diseases. High-resolution computed tomography (HRCT) has been the modality of choice in the radiologic diagnosis of PLC. Imaging features of PLC on HRCT include thickening of interlobular septa, fissures, and bronchovascular bundles. Distribution of PLC may be focal or diffuse, unilateral or bilateral, and symmetric or asymmetric. Although FDG-PET has been extensively used in primary or secondary lung malignancies, its role and appearance in PLC have not been well determined in the literature. In this communication, we describe a spectrum of FDG-PET and CT findings in 5 cases with PLC. Similar to CT, the distribution of PLC can be extensive or limited on the FDG-PET. Diffuse, lobar, or segmental FDG uptake in the lungs is seen in extensive PLC. In limited PLC, a linear or a hazy area of FDG uptake extending from the tumor can be seen. Recognition of various patterns related to PLC on FDG-PET may allow accurate diagnosis of disease and could potentially influence the management of these patients.

Contrast media in liver sonography: correlation with enhanced dynamic magnetic resonance imaging

Both color Doppler sonography and and magnetic resonance are imaging techniques which do not use ionizing radiations, but despite this common feature there remain many differences between them. Thus, color Doppler sonography is a cost-effective technique using mechanical waves and providing real-time images while magnetic resonance imaging is much more expensive, uses magnetic fields and radiofrequency energy and provides static images. The former method is very sensitive in detecting focal liver lesions >1 cm, but its specificity in characterization is not as good, not even with the color Doppler technique. The main differences between color Doppler sonography, with and/or without echocontrast agents, and contrast-enhanced (Gadolinium chelates) dynamic magnetic resonance imaging in focal liver lesions can be summarized as follows: (1) magnetic resonance imaging depicts tumor vascularization only after paramagnetic contrast media injection. Enhanced images completely depend upon the contrast agent and cannot be achieved without it. In contrast, color Doppler signal is not modified by the contrast agent, it just becomes stronger. (2) Contrast-enhanced magnetic resonance signal (as well as contrast-enhanced computed tomography signal) provides more pieces of information than color Doppler signal about the flow characteristics of liver nodules—i.e. it shows not only blood flow (hyper-/hypovascular nodule), but also the interstitial spread of the agent and its wash-out. For example, hepatocellular carcinoma and focal nodular hyperplasia have similar perfusion while agent spread and wash-out decrease very quickly in the former and more slowly in the latter, except for the low decrease of the central scar. (3) Color Doppler technology improvements, higher sensitivity to slow flows and better signal/noise ratio reduce the applications of contrast-enhanced sonography in focal liver lesions because the agents modify only sensitivity and not the imaging in slow flow studies. (4) The higher cost of contrast studies is justified only in selected cases, namely treatment follow-up in the lesions with rich pretreatment vascularization. Finally, the higher cost of contrast magnetic resonance studies is justified to increase sensitivity and especially to allow lesion characterization.

Pneumothorax simulated by detachment of parietal pleura associated with pneumomediastinum

We report a case of blunt chest trauma, where findings on repeated conventional chest radiographs were compatible with pneumothorax developing CT showed that the appearance was due to a detachment after 2 days of mechanical high-pressure ventilation. of the parietal pleura along the lateral, mediastinal and diaphragmatic boundaries of the lungs, imitating a pneumothorax. The widespread pleural detachment was caused by the extra-mediastinal interstitial spread of mediastinal emphysema caused by a small tear in the left main bronchus, which had initially escaped bronchoscopic detection.

Pathological studies on sarcoidosis autopsy. II. Early change, mode of progression and death pattern.

Three hundred and twenty autopsy cases of sarcoidosis in Japan were analyzed to determine the pathological changes in the early stage, the mode of progression in each organ and the changes in the final stage of the disease. The lung and the mediastinal lymph nodes were affected in most of the cases, while the lesions were limited to the lung and intrathoracic nodes in some of the cases. It was suspected that early changes developed in the lung and in the hilar, and then in the mediastinal lymph nodes. The progression of sarcoid granulomas in the lung was classified into three patterns: (i) probably of a disseminated hematogenous nature; (ii) of an interstitial lymphogenous nature; and (iii) of a local expansive nature. These three patterns were observed also in the heart. In the brain, perivascular granuloma formation was a prominent feature. In the other organs in which sarcoid lesions were not malignant nor disseminated and conglomerated, no interstitial patterns were observed. In chronic cases, repeated dissemination and particularly the interstitial spread of granulomatous changes led to a prominent interstitial fibrosis and dysfunction of the organs, finally resulting in death of the individual. In such long-standing cases, the mediastinal nodes deteriorated by hyalinous degeneration of the granulomas, and many active granulomas were formed in the intra-abdominal or body surface lymph nodes. These lymph nodes were likely to continue supplying sensitized lymphocytes to the whole body. A persistence of active change in the lymph nodes and the lymphogenous spread of granulomas in organs would appear to be key factors in the prognosis of sarcoidosis.

THE EFFECT OF THE PULSE ON THE SPREAD OF SUBSTANCES THROUGH TISSUES

The pulsation of blood vessels in the ear of the rabbit greatly increases the rate of the spread of dye introduced into the subcutaneous tissue. The appearance of edema in tissues perfused at a constant pressure leads to very little increase in the rate of dye spread. By contrast, a rapid interstitial spread of dye occurs in tissues becoming edematous while perfused with a pulsatile flow of blood. The significance of these facts is discussed.