Sirolimus and intraoperative hyperthermic peritoneal chemoperfusion with mitomycin-C do not impair healing of bowel anastomoses

Surgeons will increasingly have to address the development of gastrointestinal disease in transplant patients or deal with extended bowel resection and bowel anastomosis in advanced cancer patients. Immunosuppressants as well as intraoperative hyperthermic peritoneal chemoperfusion (IHPC) may alter intestinal anastomotic healing. We evaluated the effects of the immunosuppressant sirolimus and of IHPC on healing and stability of bowel anastomoses in pigs. Twenty-four pigs were divided into four groups (SIR: sirolimus was administered orally; IHPC: animals received IHPC with mitomycin-C; COMP: combination of sirolimus and IHPC was administered; CON: sham-treated control group). Animals underwent hand-sutured small bowel and left colon anastomoses and were killed on postoperative day 4. Anastomoses were evaluated by morphometric analysis and immunohistochemistry (IHC) and by measuring the bursting pressure (BP). In all experimental groups (SIR, IHPC, COMP), anastomotic BPs remained unaltered and were not statistically different compared with control (CON). In addition, ileum villous height and colonic crypt depth analysis revealed no significant difference in mucosal thickness, and IHC showed no difference among groups in proliferation, as assessed by the number of KI-67- and bromodeoxyuridine-labeled cells. Immunosuppression with sirolimus as well as IHPC with mitomycin-C do not alter healing of intestinal anastomosis in pigs.

Anterior Stafne's bone cavity mimicking a periapical lesion of endodontic origin: report of two cases

INTRODUCTION: This report of 2 cases describes the diagnostic procedures used to identify 2 Stafne's bone cavities (SBC) found in unusually anterior locations in the mandible, both mimicking periapical lesions of endodontic origin. METHODS: In the first patient, a 47-year-old man, an SBC was diagnosed in the area of teeth #27, 28, and 29. In the second patient, a 62-year-old man, the SBC was a fortuitous finding, because this patient was referred for dental implant therapy. RESULTS: In both cases, the final diagnosis was achieved by using limited cone beam computed tomography (CBCT) and magnetic resonance imaging (MRI). In both patients, the lingual bone cavity was found to be occupied by accessory salivary gland tissue. CONCLUSIONS: The combination of CBCT and MRI as noninvasive diagnostic techniques seems ideal to avoid surgical explorations, incisional biopsies, or enucleations of the lesion for diagnostic purposes.

Effect of peritoneal fluid from endometriosis patients on neuroblastoma cells in culture

AIM: Endometriosis is often associated with lower abdominal pain, dysmenorrhea, dyspareunia, and chronic pelvic pain. There is no correlation between the extent of endometriosis and the intensity of pain. The mechanism of pain in endometriosis is unknown. The aim of our study was to investigate the influence of peritoneal fluid (PF) from endometriosis patients on cultured neural cells that are the morphological basis of nociception, and to determine whether there was a relationship between the rAFS staging and an elevation of TGF-beta1 production by these cells. METHODS: Different human neuroblastoma cell lines were grown to 3/4 confluence and then cultured in presence of PF pooled according to the presence of no, mild, or severe endometriosis. After 6 and 24 h of incubation, the morphological changes were assessed and the metabolic activity was determined. RESULTS: The different cell lines showed strongly varying proliferation and aggregation patterns. The metabolic activity was also varying between cell lines, but no consistently increased cell turnover in the PF when compared with the control medium nor associated to a particular, endometriosis-derived PF pool could be shown. In this experimental setting, we have observed that the cell proliferation in the presence of PF was inhibited, and not enhanced as it might have been expected. Measurement of TGF-beta1 showed higher production rates for this cytokine under exposure to PF than in controls for some but not all tested cell lines, but there was no association with the stage (rAFS) of the disease. CONCLUSION: The neuronal cell culture model may become a useful tool to investigate the endometriosis-derived pain, but different endpoints and cell lines may have to be introduced.

Correlation between symptoms of pain and peritoneal fluid inflammatory cytokine concentrations in endometriosis

Endometriosis affects 10-20% of women during reproductive age and is a common cause of infertility and pain leading to work absenteeism and reduced quality of life.The objective of this study was to investigate the association between the presence and concentration of interleukin-8 (IL-8), RANTES, osteoprotegerin (OPG), pregnancy-associated plasma protein A (PAPP-A), tumour necrosis factor-alpha (TNF-alpha), midkine and glycodelin in the peritoneal fluid (PF) and the intensity of pain reported by patients undergoing laparoscopy in our clinic. They rated their pain during menstruation, intercourse and lower abdominal using a visual analogue scale. During laparoscopy, PF was aspirated. Pain scores were correlated to the concentration of the above substances in the PF and to the stage of endometriosis. Endometriosis was histologically confirmed in 41 of 68 participating women; 27 without such evidence were considered as controls. TNF-alpha and glycodelin correlated positively with the level of menstrual pain. For IL-8, RANTES, OPG and PAPP-A no correlation between their PF concentration and the menstrual pain scores was observed. Patients with severe dysmenorrhoea had increased PF cytokine and marker levels; the difference was significant for TNF-alpha and glycodelin when compared with the other patients (no or moderate pain). TNF-alpha and glycodelin may thus play a role in endometriosis and the severity of menstrual pain.

Epithelial neutrophil-activating peptide 78 concentrations are elevated in the peritoneal fluid of women with endometriosis

To investigate the presence of epithelial neutrophil-activating peptide 78 (ENA-78) in peritoneal fluid of women with and without endometriosis and to identify the cells that produce this inflammatory protein.

Blood vessel anomalities in the oral cavity of two calves

Two calves were presented with a congenital mass in the rostral mandibular gingiva. In both cases the masses relapsed after surgical removal. Histologically, the two masses were composed of irregularly arranged vascular cavities, embedded in loosely arranged stroma and alcian-blue PAS positive ground substance. Radiologically, a destruction of the alveolar cavity was recognized in both cases, which was in case 1 histologically compatible with bone resorption and remodeling associated with the infiltration of abundant granulation tissue. A literature survey revealed that no consistent criteria for a correct classification for vascular tumours exists, resulting in the fact that comparable lesions were named differently in the past. We therefore propose to classify such lesions as congential vascular malformation until distinct morphological, immunohistochemical and molecular genetic analysis criteria will exist.

Harmonic Oscillator in a 1D or 2D Cavity with General Perfectly Reflecting Walls

We investigate the simple harmonic oscillator in a 1-d box, and the 2-d isotropic harmonic oscillator problem in a circular cavity with perfectly reflecting boundary conditions. The energy spectrum has been calculated as a function of the self-adjoint extension parameter. For sufficiently negative values of the self-adjoint extension parameter, there are bound states localized at the wall of the box or the cavity that resonate with the standard bound states of the simple harmonic oscillator or the isotropic oscillator. A free particle in a circular cavity has been studied for the sake of comparison. This work represents an application of the recent generalization of the Heisenberg uncertainty relation related to the theory of self-adjoint extensions in a finite volume.

Increased levels of biglycan in endometriomas and peritoneal fluid samples from ovarian endometriosis patients

Abstract In our previous low-density-array gene-expression analysis we found an increased expression of biglycan gene in ovarian endometriosis patients. In the present study we evaluated biglycan expression at the protein level in tissue, serum and peritoneal fluid (PF) from ovarian endometriosis patients, patients with benign ovarian cysts and healthy women. Twenty samples of endometriomas and 27 of control tissues (benign ovarian cysts and eutopic endometrium of healthy women) were obtained laparoscopically or by curettage. Serum and PF samples were collected from 56 ovarian endometriosis patients and 40 controls (patients with benign cysts and healthy women). Tissue biglycan levels and serum and PF biglycan concentrations were determined by Western blotting and ELISA, respectively. Biglycan was detected in endometriomas and in benign cysts tissues but differed in glycosylation levels. The PF biglycan concentrations were significantly increased in ovarian endometriosis patients (mean ± SD = 220.3 ± 190.5 pg/mg protein) compared to the whole control group (101.9 ± 94.7 pg/mg protein, p < 0.001), while serum concentrations did not differ significantly. Biglycan appears to be involved in ovarian pathologies and probably has different roles in benign cysts as compared to ovarian endometriomas.

Correlation between altered central pain processing and concentration of peritoneal fluid inflammatory cytokines in endometriosis patients with chronic pelvic pain

Translational research has not yet elucidated whether alterations in central pain processes are related to peripheral inflammatory processes in chronic pain patients. We tested the hypothesis that the concentration of cytokines in the peritoneal fluid of endometriosis patients with chronic pain correlate with parameters of hyperexcitability of the nociceptive system. The concentrations of 15 peritoneal fluid cytokines were measured in 11 patients with chronic pelvic pain and a diagnosis of endometriosis. Six parameters assessing central pain processes were recorded. Positive correlations between concentration of some cytokines in the peritoneal fluid and amplification of central pain processing were found. The results suggest that inflammatory mechanisms may be important in the pathophysiology of altered central pain processes and that cytokines produced in the environment of endometriosis could act as mediators between the peripheral lesion and changes in central nociceptive processes.

Long-term results of a prospective randomised trial assessing the impact of readaptation of the dorsolateral peritoneal layer following extended pelvic lymph node dissection and cystectomy.

OBJECTIVE To evaluate the long term oncological and functional outcomes after readaptation of the dorsolateral peritoneal layer following pelvic lymph node dissection (PLND) and cystectomy . PATIENTS AND METHODS A randomised, single-center, single-blinded, two-arm trial was conducted on 200 consecutive cystectomy patients who underwent PLND and cystectomy for bladder cancer (peritoneal layer (n=100; 73 male, 27 female; median age 68 yrs, range 35-86 yrs) and group B without readapation (n=100; 66 male, 34 female; median age 65 yrs, range 30-86 yrs). Regular postoperative follow-up was performed at our outpatient clinic. Median follow-up was 59 months (range 3-100 months), five patients were lost to follow-up in group A, seven in group B. Bowel function was evaluated using the validated Gastrointestinal Quality of Life Index questionnaire and an institutional questionnaire regarding post-cystectomy outcome. Local recurrences and distal metastases were evaluated using computed tomography and bone scan at the regular follow-up visits. RESULTS There was no significant difference between the two groups in terms of the rate of local (pelvic) recurrence (5/95 [5.3%] in group A; 7/93 [7.5%] in group B; p = 0.53), the rate of distant metastases (21/95 [22.1%] in group A; 23/93 [24.7%] in group B; p = 0.67), cancer-specific survival (p = 0.37), and overall survival (p = 0.59). Group A had significantly better bowel function at 3 (p < 0.001), 6 (p < 0.006), 12 (p <0.006) and 24 months (p = 0.04), and significantly less postoperative abdominal pain and bloating at 3 (p = 0.002) and 6 months (p = 0.01). CONCLUSION Readaptation of the dorsolateral peritoneal layer following PLND and cystectomy has a beneficial long-term impact on bowel function and postoperative pain without compromising oncological radicality. This article is protected by copyright. All rights reserved.

Phospholipase A2 group IIA is elevated in endometriomas but not in peritoneal fluid and serum of ovarian endometriosis patients.

Our previous gene expression analysis identified phospholipase A2 group IIA (PLA2G2A) as a potential biomarker of ovarian endometriosis. The aim of this study was to evaluate PLA2G2A mRNA and protein levels in tissue samples (endometriomas and normal endometrium) and in serum and peritoneal fluid of ovarian endometriosis patients and control women. One-hundred and sixteen women were included in this study: the case group included 70 ovarian endometriosis patients, and the control group included 38 healthy women and 8 patients with benign ovarian cysts. We observed 41.6-fold greater PLA2G2A mRNA levels in endometrioma tissue, compared to normal endometrium tissue. Using Western blotting, PLA2G2A was detected in all samples of endometriomas, but not in normal endometrium, and immunohistochemistry showed PLA2G2A-specific staining in epithelial cells of endometrioma paraffin sections. However, there were no significant differences in PLA2G2A levels between cases and controls according to ELISA of peritoneal fluid (6.0 ± 4.4 ng/ml, 6.6 ± 4.3 ng/ml; p = 0.5240) and serum (2.9 ± 2.1 ng/ml, 3.1 ± 2.2 ng/ml; p = 0.7989). Our data indicate that PLA2G2A is implicated in the pathophysiology of ovarian endometriosis, but that it cannot be used as a diagnostic biomarker.

Fate of accidental symmetries of the relativistic hydrogen atom in a spherical cavity

The non-relativistic hydrogen atom enjoys an accidental SO(4) symmetry, that enlarges the rotational SO(3) symmetry, by extending the angular momentum algebra with the Runge–Lenz vector. In the relativistic hydrogen atom the accidental symmetry is partially lifted. Due to the Johnson–Lippmann operator, which commutes with the Dirac Hamiltonian, some degeneracy remains. When the non-relativistic hydrogen atom is put in a spherical cavity of radius R with perfectly reflecting Robin boundary conditions, characterized by a self-adjoint extension parameter γ, in general the accidental SO(4) symmetry is lifted. However, for R=(l+1)(l+2)a (where a is the Bohr radius and l is the orbital angular momentum) some degeneracy remains when γ=∞ or γ = 2/R. In the relativistic case, we consider the most general spherically and parity invariant boundary condition, which is characterized by a self-adjoint extension parameter. In this case, the remnant accidental symmetry is always lifted in a finite volume. We also investigate the accidental symmetry in the context of the Pauli equation, which sheds light on the proper non-relativistic treatment including spin. In that case, again some degeneracy remains for specific values of R and γ.