scholarly journals Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC): increased intraperitoneal pressure does not affect distribution patterns but leads to deeper penetration depth of doxorubicin in a sheep model

2021 ◽  
Author(s):  
Myriam Mimouni ◽  
Christophe Richard ◽  
Pierre Adenot ◽  
Martine Letheule ◽  
Anne Tarrade ◽  
...  

Abstract Background Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is an innovative treatment against peritoneal carcinomatosis. Doxorubicin is a common intra-venous chemotherapy used for peritoneal carcinomatosis and for PIPAC. This study evaluated the impact of increased PIPAC intraperitoneal pressure on the distribution and cell penetration of doxorubicin in a sheep model. Methods Doxorubicin was aerosolized using PIPAC into the peritoneal cavity of 6 ewes: N=3 with 12mmHg intraperitoneal pressure (group 1) and N=3 with 20mmHg (group 2). Samples from peritoneum (N=6), ovarian (N=1), omentum (N=1) and caecum (N=1) were collected for each ewe. The number of doxorubicin positive cells was determined using the ratio between doxorubicine fluorescence-positive cell nuclei (DOXO+) over total number of DAPI positive cell nuclei (DAPI+). Penetration depth (μm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei over the total number of cell nuclei that were stained with DAPI. Penetration depth (μm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei. Results DOXO+ nuclei were identified in 87% of samples. All omental samples, directly localized in front of the nebulizer head, had 100% DOXO+ nuclei whereas very few nuclei were DOXO+ for caecum. Distribution patterns were not different between the two groups but penetration depth in ovary and caecum samples was significantly deeper in group 2. Conclusions This study showed that applying a higher intra-peritoneal pressure during PIPAC treatment leads to a deeper penetration of doxorubicin in ovarian and caecum but does not affect distribution patterns.

2020 ◽  
Author(s):  
Myriam Mimouni ◽  
Christophe Richard ◽  
Pierre Adenot ◽  
Martine Letheule ◽  
Anne Tarrade ◽  
...  

Abstract Background:Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is an innovative treatment against peritoneal carcinomatosis. Doxorubicin is a common intra-venous chemotherapy used for peritoneal carcinomatosis and for PIPAC. This study evaluated the impact of increased PIPAC intraperitoneal pressure on the distribution and cell penetration of doxorubicin in a sheep model.Methods: Doxorubicin was aerosolized using PIPAC into the peritoneal cavity of 6 ewes (pre-alpes breed): N=3 with 12mmHg intraperitoneal pressure (group 1) and N=3 with 20mmHg (group 2). Samples from peritoneum (N=6), ovarian (N=1), omentum (N=1) and caecum (N=1) were collected for each ewe. The number of doxorubicin positive cells was determined using the ratio between doxorubicine fluorescence-positive cell nuclei (DOXO+) over total number of DAPI positive cell nuclei (DAPI+). Penetration depth (μm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei over the total number of cell nuclei that were stained with DAPI. Penetration depth (μm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei.Results: DOXO+ nuclei were identified in 87% of samples. All omental samples, directly localized in front of the nebulizer head, had 100% DOXO+ nuclei whereas very few nuclei were DOXO+ for caecum. Distribution patterns were not different between the two groups but penetration depth in ovary and caecum samples was significantly deeper in group 2. Conclusions:This study showed that applying a higher intra-peritoneal pressure during PIPAC treatment leads to a deeper penetration of doxorubicin in ovarian and caecum but does not affect distribution patterns.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Myriam Mimouni ◽  
Christophe Richard ◽  
Pierre Adenot ◽  
Martine Letheule ◽  
Anne Tarrade ◽  
...  

Abstract Background Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is an innovative treatment against peritoneal carcinomatosis. Doxorubicin is a common intra-venous chemotherapy used for peritoneal carcinomatosis and for PIPAC. This study evaluated the impact of increased PIPAC intraperitoneal pressure on the distribution and cell penetration of doxorubicin in a sheep model. Methods Doxorubicin was aerosolized using PIPAC into the peritoneal cavity of 6 ewes (pre-alpes breed): N = 3 with 12 mmHg intraperitoneal pressure (“group 12”) and N = 3 with 20 mmHg (“group 20”). Samples from peritoneum (N = 6), ovarian (N = 1), omentum (N = 1) and caecum (N = 1) were collected for each ewe. The number of doxorubicin positive cells was determined using the ratio between doxorubicine fluorescence-positive cell nuclei (DOXO+) over total number of DAPI positive cell nuclei (DAPI+). Penetration depth (μm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei over the total number of cell nuclei that were stained with DAPI. Penetration depth (μm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei. Results DOXO+ nuclei were identified in 87% of samples. All omental samples, directly localized in front of the nebulizer head, had 100% DOXO+ nuclei whereas very few nuclei were DOXO+ for caecum. Distribution patterns were not different between the two groups but penetration depth in ovary and caecum samples was significantly deeper in group 20. Conclusions This study showed that applying a higher intra-peritoneal pressure during PIPAC treatment leads to a deeper penetration of doxorubicin in ovarian and caecum but does not affect distribution patterns.


2009 ◽  
Vol 11 (5) ◽  
pp. 547-554 ◽  
Author(s):  
Halit Çavuşoğlu ◽  
Cengiz Tuncer ◽  
Canan Tanik ◽  
Zihni Mutlu ◽  
Ebruhan Zengin ◽  
...  

Object Postoperative dysphagia is a well-recognized complication of the anterior surgical approach to the cervical spine. However, its incidence and etiology remain unknown. The aim of this study was to investigate the impact of automatic retractor use on the esophagus and to describe the related pathological changes that might occur during cervical spine surgery. Methods A single-level cervical discectomy was performed via an anterior approach in 16 skeletally mature female sheep. Continuous retraction was applied with an automatic retractor system during surgery. The sheep model was chosen because of anatomical similarities to the human esophagus. The esophageal tract in every animal was examined using contrast radiographic examination. Eight animals were killed 3 days after the operation (Group 1). The remaining sheep were killed 4 weeks after the operation (Group 2). The esophagi were removed for histopathological study, which was performed using H & E and Masson trichrome staining. The changes in esophageal innervation were examined with nicotinamide adenine dinucleotide diphosphate–diaphorase histochemical staining. Results Only 1 animal (a Group 1 sheep) demonstrated any postoperative radiographic abnormality. In Group 1 sheep, histopathological study of the esophagi at the treated level revealed edema between the muscular fibers in the outer longitudinal and inner circular layers of the muscularis propria. At some points, obvious signs of vascular congestion, vascular damage, and inflammation were observed. In the Group 2 animals, there was mild-to-moderate fibrosis extending from the outer surface of the esophagus to the longitudinal layers of the muscularis propria in the area to which retraction had been applied. Enzyme-histochemical staining revealed the presence of normal myenteric plexus and ganglion cells, and nitrergic innervation in all parts of the esophagus wall. Conclusions The results of this study demonstrate that direct pressure induced by the medial retractor blade on the esophagus wall leads to local injury. Postoperative dysphagia in human patients who have undergone anterior cervical spine surgery could be a clinical manifestation of this phenomenon.


Author(s):  
Hossam Ebaid ◽  
Mohamed Habila ◽  
Iftekhar Hassan ◽  
Jameel Al-Tamimi ◽  
Mohamed S. Omar ◽  
...  

Background: Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl4 challenge. Results: Administration of CCL4 resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL4 challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that CCl4 challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPs-curcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%. Conclusion: Administration of AgNPs-curcumin resulted in significant antioxidant activity in vivo. This agent has the potential to prevent the hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Jerzy Stanek

AbstractShort CommunicationsEXIT (ex-utero intrapartum treatment) procedure is a fetal survival-increasing modification of cesarean section. Previously we found an increase incidence of fetal vascular malperfusion (FVM) in placentas from EXIT procedures which indicates the underlying stasis of fetal blood flow in such cases. This retrospective analysis analyzes the impact of the recently introduced CD34 immunostain for the FVM diagnosis in placentas from EXIT procedures.Objectives and MethodsA total of 105 placentas from EXIT procedures (48 to airway, 43 to ECMO and 14 to resection) were studied. In 73 older cases, the placental histological diagnosis of segmental FVM was made on H&E stained placental sections only (segmental villous avascularity) (Group 1), while in 32 most recent cases, the CD34 component of a double E-cadherin/CD34 immunostain slides was also routinely used to detect the early FVM (endothelial fragmentation, villous hypovascularity) (Group 2). 23 clinical and 47 independent placental phenotypes were compared by χ2 or ANOVA, where appropriate.ResultsThere was no statistical significance between the groups in rates of segmental villous avascularity (29 vs. 34%), but performing CD34 immunostain resulted in adding and/or upgrading 12 more cases of segmental FVM in Group 2, thus increasing the sensitivity of placental examination for FVM by 37%. There were no other statistically significantly differences in clinical (except for congenital diaphragmatic hernias statistically significantly more common in Group 2, 34 vs 56%, p=0.03) and placental phenotypes, proving the otherwise comparability of the groups.ConclusionsThe use of CD34 immunostain increases the sensitivity of placental examination for FVM by 1/3, which may improve the neonatal management by revealing the increased likelihood of the potentially life-threatening neonatal complications.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Francesco A. Ciarleglio ◽  
Marta Rigoni ◽  
Liliana Mereu ◽  
Cai Tommaso ◽  
Alessandro Carrara ◽  
...  

Abstract Background The aim of this retrospective comparative study was to assess the impact of COVID-19 and delayed emergency department access on emergency surgery outcomes, by comparing the main clinical outcomes in the period March–May 2019 (group 1) with the same period during the national COVID-19 lockdown in Italy (March–May 2020, group 2). Methods A comparison (groups 1 versus 2) and subgroup analysis were performed between patients’ demographic, medical history, surgical, clinical and management characteristics. Results Two-hundred forty-six patients were included, 137 in group 1 and 109 in group 2 (p = 0.03). No significant differences were observed in the peri-operative characteristics of the two groups. A declared delay in access to hospital and preoperative SARS-CoV-2 infection rates were 15.5% and 5.8%, respectively in group 2. The overall morbidity (OR = 2.22, 95% CI 1.08–4.55, p = 0.03) and 30-day mortality (OR = 1.34, 95% CI 0.33–5.50, =0.68) were significantly higher in group 2. The delayed access cohort showed a close correlation with increased morbidity (OR = 3.19, 95% CI 0.89–11.44, p = 0.07), blood transfusion (OR = 5.13, 95% CI 1.05–25.15, p = 0.04) and 30-day mortality risk (OR = 8.00, 95% CI 1.01–63.23, p = 0.05). SARS-CoV-2-positive patients had higher risk of blood transfusion (20% vs 7.8%, p = 0.37) and ICU admissions (20% vs 2.6%, p = 0.17) and a longer median LOS (9 days vs 4 days, p = 0.11). Conclusions This article provides enhanced understanding of the effects of the COVID-19 pandemic on patient access to emergency surgical care. Our findings suggest that COVID-19 changed the quality of surgical care with poorer prognosis and higher morbidity rates. Delayed emergency department access and a “filter effect” induced by a fear of COVID-19 infection in the population resulted in only the most severe cases reaching the emergency department in time.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii440-iii440
Author(s):  
Harriet Dulson ◽  
Rachel McAndrew ◽  
Mark Brougham

Abstract INTRODUCTION Children treated for CNS tumours experience a very high burden of adverse effects. Platinum-based chemotherapy and cranial radiotherapy can cause ototoxicity, which may be particularly problematic in patients who have impaired vision and cognition as a result of their tumour and associated treatment. This study assessed the prevalence of impaired hearing and vision and how this may impact upon education. METHODS 53 patients diagnosed with solid tumours in Edinburgh, UK between August 2013–2018 were included in the study. Patients were split into three groups according to treatment received: Group 1 – cisplatin-based chemotherapy and cranial radiotherapy; Group 2 - platinum-based chemotherapy, no cranial radiotherapy; Group 3 – benign brain tumours treated with surgery only. Data was collected retrospectively from patient notes. RESULTS Overall 69.5% of those treated with platinum-based chemotherapy experienced ototoxicity as assessed by Brock grading and 5.9% of patients had reduced visual acuity. Patients in Group 1 had the highest prevalence of both. 44.4% of patients in Group 1 needed increased educational support following treatment, either with extra support in the classroom or being unable to continue in mainstream school. 12.5% of Group 2 patients required such support and 31.3% in Group 3. CONCLUSIONS Children with CNS tumours frequently require support for future education but those treated with both platinum-based chemotherapy and cranial radiotherapy are at particular risk, which may be compounded by co-existent ototoxicity and visual impairment. It is essential to provide appropriate support for this patient cohort in order to maximise their educational potential.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Liu ◽  
Jing Li ◽  
Wanyu Zhang ◽  
Yihong Guo

AbstractOestradiol, an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization-embryo transfer (IVF-ET) cycles. A supraphysiologic E2 level is inevitable during controlled ovarian hyper-stimulation (COH), and its effect on the outcome of IVF-ET is controversial. The aim of this retrospective study is to evaluate the association between elevated serum oestradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and neonatal birthweight after IVF-ET cycles. The data of 3659 infertile patients with fresh IVF-ET cycles were analysed retrospectively between August 2009 and February 2017 in First Hospital of Zhengzhou University. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels ≤ 1000 pg/mL, n = 230), group 2 (serum E2 levels between 1001 and 2000 pg/mL, n = 524), group 3 (serum E2 levels between 2001 and 3000 pg/mL, n = 783), group 4 (serum E2 levels between 3001 and 4000 pg/mL, n = 721), group 5 (serum E2 levels between 4001 and 5000 pg/mL, n = 548 ), and group 6 (serum E2 levels > 5000 pg/mL, n = 852). Univariate linear regression was used to evaluate the independent correlation between each factor and outcome index. Multiple logistic regression was used to adjust for confounding factors. The LBW rates were as follows: 3.0% (group 1), 2.9% (group 2), 1.9% (group 3), 2.9% (group 4), 2.9% (group 5), and 2.0% (group 6) (P = 0.629), respectively. There were no statistically significant differences in the incidences of neonatal LBW among the six groups. We did not detect an association between peak serum E2 level during ovarian stimulation and neonatal birthweight after IVF-ET. The results of this retrospective cohort study showed that serum E2 peak levels during ovarian stimulation were not associated with birth weight during IVF cycles. In addition, no association was found between higher E2 levels and increased LBW risk. Our observations suggest that the hyper-oestrogenic milieu during COS does not seem to have adverse effects on the birthweight of offspring after IVF. Although this study provides some reference, the obstetric-related factors were not included due to historical reasons. The impact of the high estrogen environment during COS on the birth weight of IVF offspring still needs future research.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 340.2-341
Author(s):  
V. Orefice ◽  
F. Ceccarelli ◽  
C. Barbati ◽  
R. Lucchetti ◽  
G. Olivieri ◽  
...  

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease mainly affecting women of childbearing age. The interplay between genetic and environmental factors may contribute to disease pathogenesis1. At today, no robust data are available about the possible contribute of diet in SLE. Caffeine, one of the most widely consumed products in the world, seems to interact with multiple components of the immune system by acting as a non-specific phosphodiesterase inhibitor2.In vitrodose-dependent treatment with caffeine seems to down-regulate mRNA levels of key inflammation-related genes and similarly reduce levels of different pro-inflammatory cytokines3.Objectives:We evaluated the impact of caffeine consumption on SLE-related disease phenotype and activity, in terms of clinimetric assessment and cytokines levels.Methods:We performed a cross-sectional study, enrolling consecutive patients and reporting their clinical and laboratory data. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2k)4. Caffeine intake was evaluated by a 7-day food frequency questionnaire, including all the main sources of caffeine. As previously reported, patients were divided in four groups according to the daily caffeine intake: <29.1 mg/day (group 1), 29.2-153.7 mg/day (group 2), 153.8-376.5 mg/day (group 3) and >376.6 mg/day (group 4)5. At the end of questionnaire filling, blood samples were collected from each patient to assess cytokines levels. These were assessed by using a panel by Bio-Plex assays to measure the levels of IL-6, IL-10, IL-17, IL-27, IFN-γ, IFN-α and Blys.Results:We enrolled 89 SLE patients (F/M 87/2, median age 46 years, IQR 14; median disease duration 144 months, IQR 150). The median intake of caffeine was 195 mg/day (IQR 160.5). At the time of the enrollment, 8 patients (8.9%) referred a caffeine intake < 29.1 mg/day (group 1), 27 patients (30.3%) between 29.2 and 153.7 mg/day (group 2), 45 patients (51%) between 153.8 and 376.5 mg/day (group 3) and 9 patients (10.1%) >376.6 mg/day (group 4). A negative correlation between the levels of caffeine and disease activity, evaluated with SLEDAI-2K, was observed (p=0.01, r=-0.26). By comparing the four groups, a significant higher prevalence of lupus nephritis, neuropsychiatric involvement, haematological manifestations, hypocomplementemia and anti-dsDNA positivity was observed in patients with less intake of caffeine (figure 1 A-E). Furthermore, patients with less intake of caffeine showed a significant more frequent use of glucocorticoids [group 4: 22.2%,versusgroup 1 (50.0%, p=0.0001), group 2 (55.5%, p=0.0001), group 3 (40.0%, p=0.009)]. Moving on cytokines analysis, a negative correlation between daily caffeine consumption and serum level of IFNγ was found (p=0.03, r=-0.2) (figure 2A); furthermore, patients with more caffeine intake showed significant lower levels of IFNα (p=0.02, figure 2B), IL-17 (p=0.01, figure 2C) and IL-6 (p=0.003, figure 2D).Conclusion:This is the first report demonstrating the impact of caffeine on SLE disease activity status, as demonstrated by the inverse correlation between its intake and both SLEDAI-2k values and cytokines levels. Moreover, in our cohort, patients with less caffeine consumption seems to have a more severe disease phenotype, especially in terms of renal and neuropsychiatric involvement. Our results seem to suggest a possible immunoregulatory dose-dependent effect of caffeine, through the modulation of serum cytokine levels, as already suggested byin vitroanalysis.References:[1]Kaul et alNat. Rev. Dis. Prim.2016; 2. Aronsen et alEurop Joul of Pharm2014; 3. Iris et alClin Immun.2018; 4. Gladman et al J Rheumatol. 2002; 5. Mikuls et alArth Rheum2002Disclosure of Interests:Valeria Orefice: None declared, Fulvia Ceccarelli: None declared, cristiana barbati: None declared, Ramona Lucchetti: None declared, Giulio Olivieri: None declared, enrica cipriano: None declared, Francesco Natalucci: None declared, Carlo Perricone: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, Fabrizio Conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi


2019 ◽  
Vol 81 (1-2) ◽  
pp. 81-86
Author(s):  
Pierre Koskas ◽  
Mouna Romdhani ◽  
Olivier Drunat

As commonly happens in epidemiological research, none of the reported studies were totally free of methodological problems. Studies have considered the influence of social relationships on dementia, but the mechanisms underlying these associations are not perfectly understood. We look at the possible impact of selection bias. For their first memory consultation, patients may come alone or accompanied by a relative. Our objective is to better understand the impact of this factor by retrospective follow-up of geriatric memory outpatients over several years. All patients over 70 who were referred to Bretonneau Memory Clinic for the first time, between January 2006 and 2018, were included in the study. The patients who came alone formed group 1, the others, whatever type of relative accompanied them, formed group 2. We compared the Mini-Mental State Examination (MMSE) scores of patients; and for all patients who came twice for consultation with at least a 60-day interval, we compared their first MMSE with the MMSE performed at the second consultation. In total, 2,935 patients were included, aged 79.7 ± 8.4 years. Six hundred and twenty-five formed group 1 and 2,310 group 2. We found a significant difference in MMSE scores between the 2 groups of patients; and upon second consultation in group 2, but that difference was minor in group 1. Our finding of a possible confounding factor underlines the complexity of choosing comparison groups in order to minimize selection bias while maintaining clinical relevance.


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