Purpose
In the treatment of breast cancer, neo-adjuvant chemotherapy is often used as systemic treatment followed by tumor excision. In this context, planning the operation with regard to excision ...margins relies on tumor size measured by MRI. The actual tumor size can be determined through pathologic evaluation. The aim of this study is to investigate the correlation and agreement between pre-operative MRI and postoperative pathological evaluation.
Methods
One hundred and ninety-three breast cancer patients that underwent neo-adjuvant chemotherapy and subsequent breast surgery were retrospectively included between January 2013 and July 2016. Preoperative tumor diameters determined with MRI were compared with postoperative tumor diameters determined by pathological analysis. Spearman correlation and Bland–Altman agreement methods were used. Results were subjected to subgroup analysis based on histological subtype (ER, HER2, ductal, lobular).
Results
The correlation between tumor size at MRI and pathology was 0.63 for the whole group, 0.39 for subtype ER + /HER2−, 0.51 for ER + /HER2 + , 0.63 for ER−/HER2 +, and 0.85 for ER−/HER2−. The mean difference and limits of agreement (LoA) between tumor size measured MRI vs. pathological assessment was 4.6 mm (LoA −27.0–36.3 mm,
n
= 195). Mean differences and LoA for subtype ER + /HER2− was 7.6 mm (LoA −31.3–46.5 mm,
n
= 100), for ER + /HER2 + 0.9 mm (LoA −8.5–10.2 mm,
n
= 33), for ER−/HER2+ −1.2 mm (LoA −5.1–7.5 mm,
n
= 21), and for ER−/HER− −0.4 mm (LoA −8.6–7.7 mm,
n
= 41).
Conclusion
HER2 + and ER−/HER2− tumor subtypes showed clear correlation and agreement between preoperative MRI and postoperative pathological assessment of tumor size. This suggests that MRI evaluation could be a suitable predictor to guide the surgical approach. Conversely, correlation and agreement for ER + /HER2− and lobular tumors was poor, evidenced by a difference in tumor size of up to 5 cm. Hence, we demonstrate that histological tumor subtype should be taken into account when planning breast conserving surgery after NAC.
Objective.Conflicting data exist on IL-6 production by human papillomavirus (HPV) immortalized cell lines and several cervical carcinoma cell lines. However, no information has been reported on the ...levels of cytokines in cervicovaginal washings in relation to cervical neoplasia. The aim of this study was to investigate whether local production of IL-6 could be found and whether the level of this cytokine was related to the severity of cervical neoplasia. IL-8 was measured to obtain additional information on an inflammatory cytokine with possible epithelial origin.
Methods.Cervicovaginal washings and sera were obtained from 35 patients with invasive cervical cancer, 62 patients with cervical intraepithelial neoplasia (CIN), and 25 control subjects. IL-6 and IL-8 levels were determined by ELISA. HPV DNA in cervical smears was detected by a HPV-16-specific PCR method and additionally by CPI/IIG PCR. Histological analysis of the inflammatory infiltrate was performed on hematoxylin–eosin-stained tissue sections.
Results.In the patients with cervical cancer, those with CIN, and the controls, the median IL-6 concentration in cervicovaginal washings was 171 pg/ml (interquartile range: 54–780), 22 pg/ml (<2–73), and < 2 pg/ml (<2–<2), respectively. For IL-8, the levels were 2756 pg/ml (1651–7107), 489 pg/ml (248–1158), and 631 pg/ml (346–897), respectively. In most subjects the local levels were much higher than in serum. Local IL-6 and IL-8 levels were significantly higher in patients with cervical carcinoma compared with CIN patients and controls. Likewise, local IL-6 levels were increased in patients with CIN compared with controls. No relation was found between cytokine levels and CIN grade or between cytokine levels and the inflammatory infiltrate scored by histological analysis.
Conclusions.There is local production of IL-6 and IL-8 in cervicovaginal secretions, and the production of IL-6 was related to the severity of cervical neoplasia.
Background & Aims: Regulatory CD4+ cells secreting the anti-inflammatory cytokine interleukin (IL)-10 play a key role in maintaining the immune balance in the intestinal mucosa. In this study we ...engineered primary CD4+ cells to express IL-10 and investigated the efficacy of this approach in offering protection against experimental colitis. Methods: Spleen-derived CD4+ cells were transduced by using a retroviral vector to simultaneously express IL-10 and green fluorescent protein (GFP). The therapeutic benefit of CD4+ cells transduced with IL-10 GFP was studied in experimental colitis, induced by transfer of CD45RBhigh CD4+ cells to severe combined immunodeficient mice, and in acute trinitrobenzene sulfonic acid (TNBS)–induced colitis. Results: Transferred engineered GFP fluorescent cells were detected for at least 15 weeks in peripheral blood, spleens, colon, and lymph nodes draining the intestine of recipient SCID mice. IL-10–GFP CD4+ cells prevented CD45RBhigh-induced transfer colitis effectively, whereas no effect was observed after transfer of nontransduced CD4+ cells. IL-10–GFP CD45RBhigh CD4+ cells lost the capacity to induce colitis. By contrast, no therapeutic benefit was observed in TNBS-induced colitis. Conclusions: Primary murine CD4+ cells that were engineered to express IL-10 by retroviral transduction act as regulatory cells in CD45RBhigh-induced transfer colitis. This approach may induce long-term maintenance of mucosal immune homeostasis in Crohn's disease.
GASTROENTEROLOGY 2002;123:1865-1876
Human papillomavirus (HPV) infections play an important role in the development of cervical neoplasia. To get to a better understanding of the role of cytokines in the development of these ...neoplasias, we analysed the presence of various cytokines in cervicovaginal washings of healthy volunteers (n=22), cervical intraepithelial neoplasia (CIN) patients (n=63) and cervical cancer patients (n=33). IL-12p40, IL-10, TGF-β1, TNF-α and IL-1β levels were significantly higher in patients with cervical cancer than in controls and CIN patients. The levels of IFN-γ were not different. Our data demonstrate alterations in the local cervical immune environment in cervical cancer patients. This could have important consequences for the further development of immune modulating therapies and vaccination strategies.
Spinal prostaglandin synthesis has been implicated in acute pain processes and in generation and maintenance of central sensitization, and intrathecal injection of cyclo-oxygenase (COX) inhibitors ...produce antinociception and reduce hypersensitivity in animals. We herein report a Phase I safety assessment of intrathecal injection of the COX inhibitor, ketorolac, in healthy volunteers, and demonstrate no serious side effects. Preclinical studies suggest a major site of action of COX inhibitors for analgesia lies in the central nervous system, especially the spinal cord. For example, COX isoenzymes are expressed in the spinal cord, acute noxious stimuli and inflammation increase spinal prostaglandin production, and spinally administered prostaglandins excite dorsal horn projection neurons, induce release of excitatory neurotransmitters, and cause nociceptive behavior. Intrathecal injection of COX inhibitors increases thermal and mechanical withdrawal threshold in animals with inflammation or nerve injury at doses several 100-fold less than those required systemically. Following pre-clinical neurotoxicity screening and regulatory agency approval, we examined the safety of intrathecal injection of a preservative-free formulation of the COX inhibitor, ketorolac. In an open label, dose-escalating design, 20 healthy volunteers received intrathecal ketorolac, 0.25, 0.5, 1, or 2mg (n=5 per group). Ketorolac did not alter blood pressure, although there was small (10-12%), dose-independent reduction in heart rate for the first hour after injection when data from all subjects were pooled. Ketorolac did not affect sensory or motor function or deep tendon reflexes, and there were no subjective sensations, neurologic or otherwise, reported by the volunteers. Ketorolac did not reduce pain report to heat stimuli applied to the lateral calf. One subject had a mild headache 24h after study, resolving the next day. There were no long-term side effects 6 months after study. These data suggest that intrathecal ketorolac does not produce a high incidence of serious adverse events, and they support further investigation for analgesia.
Purpose: Cooling muscles might produce a temporary reduction of spasticity. This study investigated muscle coordination in spasticity under the influence of cooling. Methods: A repetitive movement ...(RM-) test of the ankle was used, while measuring the angle and surface-electromyography (EMG) of the m. tibialis anterior and m. triceps surae. Ensemble averaging provided quantified measures of muscle activation. Sixteen patients with spasticity in their lower extremity due to stroke or spinal cord injury participated in the study. Physical examination and the RM-test was done before and after cooling the m. triceps surae for 20 minutes by coldpacks. Results: The results show that Achilles hyperreflexia and clonus were abolished in all, and all but one patient, respectively. The EMG of the m. triceps surae, acting as a prime mover, was increased (p 0.028). However, this improved muscle coordination resulted in just a slightly increased active range of motion (less than 2 degrees at p 0.049). Conclusion: Apparently, the increase in excitability of the alpha motoneuron pool in voluntary movements of patients with spasticity is not followed by an improvement in the ability to move.
Background: Interleukin-10 (IL-10) is an anti-inflammatory cytokine that downregulates the secretion of pro-inflammatory cytokines and additionally induces the secretion of anti-inflammatory ...cytokines, thus possibly leading to reduction of chronic inflammation in inflammatory bowel disease. In this study we evaluated the anti-inflammatory effect of IL-10 in a model of acute colitis in rabbits. Methods
To assess the anti-inflammatory action of lexipafant (BB-882), a platelet activating factor antagonist, in an animal model of acute colitis.
An animal intervention study.
Following the rectal ...instillation of formalin 0.75% into male New Zealand White (NZW) rabbits, 0.85 ml of aggregated immunoglobulin was administered i.v. Treatment groups (0.8 mg/kg, n = 6; 2.4 mg/kg, n = 13; 3.2 mg/kg, n = 10) were given bolus doses of BB-882 two-hourly i.v. (control group, n = 25). Rectal dialysis was performed before induction of colitis and sacrifice. Dialysate leukotriene B4 (LTB4), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) levels were determined. Tissue was saved for histology and measurement of myeloperoxidase content.
There was a dose-dependent improvement in macroscopic scores (2.4 and 3.2 mg/kg: P < 0.02, P < 0.001) and myeloperoxidase levels (3.2 mg/kg: P < 0.04). Dialysate LTB4 levels fell (2.4 and 3.2 mg/kg: P < 0.03, P < 0.02) as did PGE2 levels. TXB2 concentrations remained unaffected.
The PAF receptor antagonist BB-882 shows efficacy in treating inflammation in an animal model of acute colitis as evidenced by a dose-dependent fall in macroscopic mucosal damage, neutrophil infiltration and reduced generation of inflammatory mediators.
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