Fluid-filled Body Research Articles

Abstract 3832: Fluid-overload associated large B-cell lymphoma and determinants of outcomes: Analysis of a pooled database

Abstract Background: Fluid overload-associated large B-cell lymphoma (FOLBCL) is a new WHO lymphoma entity previously known as PEL-like lymphoma or HHV8-unrelated PEL-like lymphoma. It is a rare lymphoma that arises within fluid-filled body cavities without a solid component. FOLBCL occurs in the absence of immunodeficiency and is commonly associated with conditions associated with fluid overload. It expresses mature B-cell phenotype and occasional EBV infection markers. We conducted this study to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect outcomes in this rare and newly defined lymphoma subtype. Materials & Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 115 cases that fit the diagnostic criteria for FOLBCL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 115 patients with confirmed FOLBCL were identified. The median age was 74, with a peak incidence between 72 and 82 years. There was a male preponderance with M:F of 2. The pleural, pericardial, and peritoneal cavities were involved in 75%, 34, and 27%. The median duration of symptoms before diagnosis was 1 month. Patients presented with constitutional symptoms and hepatosplenomegaly in 13% and 1%, respectively—no patients presented with lymph node and bone marrow involvement. The median OS of the whole group was 16 months. Patients younger than 70 had better median OS than 70 and older (24 vs. 10 months, p=0.008). The presence of any malignant peritoneal effusion was associated with worse OS when compared to effusion limited to the thoracic cavity (7 vs. 24 months, p=0.005). LDH>500 was also associated with worse OS (p=0.02). Sex, the presence of fluid overload-causing conditions, and serum IL2R levels did not seem to impact OS. MYC re-arrangement had numerically worse OS when present but did not reach statistical significance. Chemotherapy demonstrated superior OS compared to no treatment (24 vs. 7 months, p=0.009). Patients who attained CR as their best response had a superior median OS (p<0.0001). Conclusion: This study presents updated clinicopathologic data from a pooled cohort of patients with FOLBCL. It identifies the age, the primary location of cavitary disease, LDH, active therapy, and quality of response to treatment as key determinants of OS. Citation Format: Philip A. Haddad, Supriya Gupta, Christopher Graham. Fluid-overload associated large B-cell lymphoma and determinants of outcomes: Analysis of a pooled database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3832.

Fluid-Overload Associated Large B-Cell Lymphoma Clinicopathologic Features and Determinants of Outcomes: Analysis of a Pooled Database

Background: Fluid overload-associated large B-cell lymphoma (FOLBCL) is a new WHO lymphoma entity previously known as PEL-like lymphoma or HHV8-unrelated PEL-like lymphoma. It is a rare lymphoma that arises within fluid-filled body cavities without a solid component. FOLBCL occurs in the absence of immunodeficiency and is commonly associated with conditions associated with fluid overload. It expresses mature B-cell phenotype and occasional EBV infection markers. We conducted this study to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect outcomes in this rare and newly-defined lymphoma subtype. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 115 cases that fit the diagnostic criteria for FOLBCL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 115 patients with confirmed FOLBCL were identified. The median age was 74, with a peak incidence between 72 and 82 years. There was a male preponderance with M:F of 2. The pleural, pericardial, and peritoneal cavities were involved in 75%, 34%, and 27%, respectively. The median duration of symptoms before diagnosis was 1 month. Patients presented with constitutional symptoms and hepatosplenomegaly in 13% and 1%, respectively-no patients presented with lymph node and bone marrow involvement. The median OS of the whole group was 16 months. Patients younger than 70 had better median OS than 70 and older (24 vs. 10 months, p=0.008). The presence of any malignant peritoneal effusion was associated with worse OS when compared to effusion limited to the thoracic cavity (7 vs. 24 months, p=0.005). LDH≥500 was also associated with worse OS (p=0.02). Sex, the presence of fluid overload-causing conditions, and serum IL2R levels did not seem to impact OS. Compared to no treatment, chemotherapy had a numerically superior OS but did not reach statistical significance (19 vs. 10 months, p=0.11). However, patients that attained CR as their best response had a superior median OS (p<0.0001). Conclusions: This study presents updated clinicopathologic data from a pooled cohort of patients with FOLBCL. It identifies the age, the primary location of cavitary disease, LDH, active therapy, and quality of response to treatment as key determinants of OS.

Pressure build-up and stress variations within the Earth\u2019s crust in the light of analogue models

Strength contrasts and spatial variations in rheology are likely to produce significant stress differences in the Εarth’s crust. The buildup and the relaxation of stresses have important consequences for the state of stress of the brittle crust, its deformational behaviour and seismicity. We performed scaled analogue experiments of a classic wedge-type geometry wherein we introduced a weak, fluid-filled body representing a low-stress heterogeneity. The experiments were coupled to direct pressure measurements that revealed significant pressure differences from their surrounding stressed matrix. The magnitude of the pressure variations is similar to the magnitude of the differential stress of the strongest lithology in the system. When rocks with negligible differential stresses are considered, their pressure can be more than twice larger than the surrounding lithostatic stress. The values of the pressure variations are consistent with the stresses that are estimated in analytical studies. This behaviour is not restricted to a particular scale or rheology, but it requires materials that are able to support different levels of stress upon deformation. For non-creeping rheological behaviours, the stress and pressure variations are maintained even after deformation ceases, implying that these stress variations can be preserved in nature over geological timescales.

Primary Effusion Lymphoma: Secretome Analysis Reveals Novel Candidate Biomarkers with Potential Pathogenetic Significance

Primary Effusion Lymphoma: Secretome Analysis Reveals Novel Candidate Biomarkers with Potential Pathogenetic Significance

Strategies of professional phagocytes in vivo: unlike macrophages, neutrophils engulf only surface-associated microbes

The early control of potentially invading microbes by our immune system primarily depends on its main professional phagocytes - macrophages and neutrophils. Although the different functions of these two cell types have been extensively studied, little is known about their respective contributions to the initial control of invading microorganisms before the onset of adaptive immune responses. The naturally translucent zebrafish larva has recently emerged as a powerful model vertebrate in which to visualise the dynamic interactions between leukocytes and microbes in vivo. Using high-resolution live imaging, we found that whereas macrophages efficiently engulf bacteria from blood or fluid-filled body cavities, neutrophils barely do so. By contrast, neutrophils very efficiently sweep up surface-associated, but not fluid-borne, bacteria. Thus the physical presentation of unopsonised microbes is a crucial determinant of neutrophil phagocytic ability. Neutrophils engulf microbes only as they move over them, in a 'vacuum-cleaner' type of behaviour. This context-dependent nature of phagocytosis by neutrophils should be of particular relevance to human infectious diseases, especially for the early phase of encounter with microbes new to the host.

Vectorial seismic modeling for 3D objects by the classical solution

The analytic benchmark solution for the scattering and diffraction of elastic P- and S-waves by a single spherical obstacle is presented in a condensed format. Our aim is divulge to the scientific community this not widely known classical solution to construct a direct seismic model for 3D objects. Some of the benchmark papers are frequently plagued by misprints and none offers results on the transient response. The treatment of the vectorial case appears to be insipient in the literature. The classical solution is a superposition of incident and diffracted fields. Plane P- or S-waves are assumed. They are expressed as expansions of spherical wave functions which are tested against exact results. The diffracted field by the obstacle is calculated from the analytical enforcing of boundary conditions at the scatterer–matrix interface. The spherical obstacle is a cavity, an elastic inclusion or a fluid-filled body. A complete set of wave functions is used in terms of Bessel and Hankel radial functions. Legendre and trigonometric functions are used for the angular coordinates. In order to provide information to calibrate and approximate the seismic modeling for real objects, results are shown in time and frequency domains. Diffracted displacements amplitudes versus normalized frequency and radiation patterns for various scatterer–matrix properties are reported. To study propagation features that may be useful to geophysicists and engineers, synthetic seismograms for some relevant cases are computed.

An IELSG International Survey of Primary Effusion Lymphoma (PEL).

PEL is a rare B-cell neoplasm characterized by a preferential involvement of fluid-filled body spaces, consistent infection of the tumor clone by human herpesvirus type-8 (HHV-8) and a close relationship with underlying immunodeficiency status of the host. The International Extranodal Lymphoma Study Group (IELSG) coordinated a retrospective survey involving 15 international institutions to determine the clinico-pathological features and patterns of outcome of PEL. Fourty-three patients (38 males and 5 females) were registered. Median age at diagnosis was 59 years (range 27–102). In 23 (53%) patients an associated human immunodeficiency virus (HIV) infection was reported, in one case the diagnosis of PEL was made after a solid organ transplantation, in two patients other immunodeficiency conditions were present. The tumor HHV-8 infection was demonstrated in 35 out of the 39 tested cases, Epstein-Barr virus infection in 13 of 30 cases. CD4 count was lower than 200/μl in 18 of the 25 cases in whom the data was available. An ECOG perfomance status score ≥ 2 was observed in 29 patients and the presence of B-symptoms in 20 patients. Serum LDH was elevated in 21 of the 39 tested patients. In 4 patients nodal involvement at diagnosis was reported, in 4 cases at least one extranodal site of localization other than serous cavities was present. A low/low-intermediate risk score according to International Prognostic Index was reported in 10 cases, an intermediate-high/high risk score in 29 cases. Twenty-one patients received systemic chemotherapy, in 17 cases an anthracycline-based regimen. Intrapleural cidofovir was administered in 3 patients. Twelve HIV+ patients received highly active anti-retroviral therapy (HAART), four of them as single therapy. Among the 39 patients for whom adequate follow-up data were available, median overall survival was 6.7 months, median cause-specific survival was 13.6 months and median progression-free survival was 8.3 months. Interestingly, cases of tumor complete regression after implementation of the sole HAART, after intrapleural administration of cidofovir or without any treatment were reported. Our data confirm the poor prognosis of PEL but suggest a possible heterogeneity of this entity with respect to its biological and clinical features. A review of the pathological, phenotypical and virological features is forthcoming to validate these preliminary results.

Amassin, an olfactomedin protein, mediates the massive intercellular adhesion of sea urchin coelomocytes.

Sea urchins have a fluid-filled body cavity, the coelom, containing four types of immunocytes called coelomocytes. Within minutes after coelomic fluid is removed from the body cavity, a massive cell–cell adhesion of coelomocytes occurs. This event is referred to as clotting. Clotting is thought to be a defense mechanism against loss of coelomic fluid if the body wall is punctured, and it may also function in the cellular encapsulation of foreign material and microbes. Here we show that this intercoelomocyte adhesion is mediated by amassin, a coelomic plasma protein with a relative molecular mass (M r) of 75 kD. Amassin forms large disulfide-bonded aggregates that adhere coelomocytes to each other. One half of the amassin protein comprises an olfactomedin (OLF) domain. Structural predictions show that amassin and other OLF domain-containing vertebrate proteins share a common architecture. This suggests that other proteins of the OLF family may function in intercellular adhesion. These findings are the first to demonstrate a function for a protein of the OLF family.

Current Status of the Tardigrada: Evolution and Ecology

The Tardigrada are bilaterally symmetrical micrometazoans with four pairs of lobopod legs terminating in claws or sucking disks. They occupy a diversity of niches in marine, freshwater, and terrestrial environments throughout the world. Some have a cosmopolitan distribution, while others are endemic. About 900 species have been described thus far, but many more species are expected as additional habitats are investigated. Most are less than 1 mm in body length and are opaque or translucent, exhibiting colors such as brown, green, orange, yellow, red, or pink in the cuticle and/or gut. Marine species are more variable in body shape and overall appearance and generally exhibit low population density with high species diversity. Reproductive modes include sexual reproduction and parthenogenesis, but much remains to be known about development. Tardigrades have a hemocoel-type of fluid-filled body cavity, a complete digestive tract, and a lobed dorsal brain with a ventral nerve cord with fused ganglia. Recent molecular analyses and additional morphological studies of the nervous system have confirmed the phylogenetic position of tardigrades as a sister group of the arthropods. The ability of tardigrades to undergo cryptobiosis has long intrigued scientists. Although tardigrades are active only when surrounded by a film of water, they can enter latent states in response to desiccation (anhydrobiosis), temperature (cryobiosis), low oxygen (anoxybiosis), and salinity changes (osmobiosis). Cryptobiotic states aid in dispersal.

Primary effusion lymphoma: A liquid phase lymphoma of fluid-filled body cavities

Primary effusion lymphoma (PEL) is a B-cell neoplasm characterized by infection of the tumor clone by human herpesvirus type-8/Kaposi's sarcoma-associated herpesvirus (HHV-8/KSHV) and by liquid growth in fluid-filled body spaces. During its entire clinical course, the lymphoma tends to remain localized to the serous body cavities with no formation of solid tumor masses. The epidemiology of PEL points to a close link with underlying immunodeficiency of the host, as most cases develop in individuals severely immunocompromised because of preexisting acquired immunodeficiency syndrome. The histogenesis and pathogenesis of PEL have been clarified to a sizeable extent by intensive investigations performed since the disease recognition in 1995. PEL is composed of postgerminal center B cells, which bridge immunoblastic and anaplastic features and typically display a non-B, non-T phenotype consistent with late stages of B-cell differentiation. HHV-8/KSHV is thought to play a major role in PEL pathogenesis via expression of several viral latent genes, which have the potential to affect B-cell growth. Other factors involved in PEL pathogenesis include deregulation of cytokine and growth factor autocrine loops, molecular alterations of the tumor DNA, cell cycle abnormalities, stimulation and selection by antigen, and infection by Epstein-Barr virus, which occurs in 70% of PEL cases. In the years since the disease discovery, the distinctiveness of the biological and clinicopathological features of PEL has prompted its recognition as an independent lymphoma category by the World Health Organization classification system of hematologic neoplasms.

Establishment of an animal-bacterial association: recruiting symbiotic vibrios from the environment.

While most animal-bacterial symbioses are reestablished each successive generation, the mechanisms by which the host and its potential microbial partners ensure tissue colonization remain largely undescribed. We used the model association between the squid Euprymna scolopes and Vibrio fischeri to examine this process. This light organ symbiosis is initiated when V. fischeri cells present in the surrounding seawater enter pores on the surface of the nascent organ and colonize deep epithelia-lined crypts. We discovered that when newly hatched squid were experimentally exposed to natural seawater, the animals responded by secreting a viscous material from the pores of the organ. Animals maintained in filtered seawater produced no secretions unless Gram-negative bacteria, either living or dead, were reintroduced. The viscous material bound only lectins that are specific for either N-acetylneuraminic acid or N-acetylgalactosamine, suggesting that it was composed of a mucus-containing matrix. Complex ciliated fields on the surface of the organ produced water currents that focused the matrix into a mass that was tethered to, and suspended above, the light organ pores. When V. fischeri cells were introduced into the seawater surrounding the squid, the bacteria were drawn into its fluid-filled body cavity during ventilation and were captured in the matrix. After residing as an aggregate for several hours, the symbionts migrated into the pores and colonized the crypt epithelia. This mode of infection may be an example of a widespread strategy by which aquatic hosts increase the likelihood of successful colonization by rarely encountered symbionts.

Glycosaminoglycans and fibrillar collagen in Priapulida: a histo- and cytochemical study.

The distribution of glycosaminoglycans and fibrillar collagen was studied in various tissues of priapulids, which represent an ancient group of marine metazoa. Sulphated glycosaminoglycans, as demonstrated at the electron microscopical level by Cupromeronic blue, were predominantly found in the cuticle, in basement membranes and also in the narrow connective tissue space below epidermis and anterior intestine. On the basis of their morphology the Cupromeronic blue precipitates could be divided into several groups. Fibrillar collagen occurred in the connective tissue under the epidermis and the epithelium of the anterior intestine. The spatial interrelationship between fibrillar collagen and glycosaminoglycans lacked with some exceptions, the high regularity found in connective tissues of other invertebrates and of vertebrates. This might be related to the special skeletal system of priapulids, consisting mainly of a strong extracellular cuticle and the turgor of the fluid-filled body cavity. In such a system the usual supportive structures seem to be of less functional significance.

MORPHOLOGICAL EFFECTS OF COBALTOUS CHLORIDE ON THE DEVELOPMENT OF LIMNAEA STAGNALIS AND LIMNAEA PALUSTRIS

1. The effect of cobaltous chloride (CoCl2) on the developmental stages of Limnaea stagnalis and L. palustris has been studied.2. Eggs and embryos were treated for 24 hours with various concentrations of CoCl2. Effective concentrations of CoCI2 ranged from 1 x 10-5 to 1 x 10-4 M for L. stagnalis and from 2 x 106 to 8 x 10-5 for L. palustris.3. Variations in resistance to CoCl2 were observed between species at the same stage of development, between eggs treated at different stages of development and between eggs from the same egg masses treated at the same stage of development.4. Treatment with CoCl2 resulted in (a) separation of blastomeres, (b) vesicular and dumbbell-shaped exogastrulae, (c) arrested gastrulae, (d) veligers with a reduced larval liver, shell and foot, and with a fluid-filled body cavity containing few mesenchyme cells, (e) shell-less snails with a reduced larval liver and shell and (f) helmet-shelled snails with abnormally wide shell apertures.5. Manganese, cadmium and nickel produced malformations similar to those caused by cobalt. The sequence of effective concentrations was Mn < Co < Cd < Ni.6. Sections of normal and cobalt-treated embryos showed an inhibition of the differentiation and proliferation of mesenchyme cells of the body and foot and an inhibition of proliferation and enlargement of the endoderm cells of the larval liver.7. Exogastrulae and hydropic exogastrulae and veliger larvae appear to be caused by an impairment in the development of the mesomeres plus a concomitant uptake of water by the blastocoel or body cavity.8. Arrested veliger larvae and the differences in their development are explained on the basis of variation in the functional capacity of their larval livers.9. The morphological evidence indicates that the several characteristic malformations result from an inhibition of the cobalt-sensitive fourth quartette of micromeres and their derivatives, the mesomeres and larval liver cells.10. The results suggest that metal ion-reactive groups in the vegetal region of the Limnaea egg may be progressively segregated into the fourth quartette of micromeres.