High-pressure intrapleural chemotherapy: feasibility in the pig model.

International audienceABSTRACT: BACKGROUND: The usual treatments for pleural malignancies are mostly palliative. In contrast, peritoneal malignancies are often treated with a curative intent by cytoreductive surgery and intraperitoneal chemotherapy. As pressure has been shown to increase antitumor efficacy, we applied the concept of high-pressure intracavitary chemotherapy to the pleural space in a swine model. METHODS: Cisplatin and gemcitabine were selected because of their antineoplasic efficacy in vitro in a wide spectrum of cancer cell lines. The pleural cavity of 21 pigs was filled with saline solution; haemodynamic and respiratory parameters were monitored. The pressure was increased to 15-25 cm H2O. This treatment was associated with pneumonectomy in 6 pigs. Five pigs were treated with chemotherapy under pressure. RESULTS: The combination of gemcitabine (100 mg/l) and cisplatin (30 mg/l) was highly cytotoxic in vitro. The maximum tolerated pressure was 20 cm H20, due to haemodynamic failure. Pneumonectomy was not tolerated, either before or after pleural infusion. Five pigs survived intrapleural chemotherapy associating gemcitabine and cisplatin with 20 cm H2O pressure for 60 min. CONCLUSIONS: High-pressure intrapleural chemotherapy is feasible in pigs. Further experiments will establish the pharmacokinetics and determine whether the benefit already shown in the peritoneum is also obtained in the pleura

Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murin model of peritoneal carcinomatosis

<p>Abstract</p> <p>Background</p> <p>The best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis.</p> <p>Methods</p> <p>Four groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured <it>in vivo </it>(tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and <it>in vitro </it>(cytotoxicity on human ovarian cancer cells).</p> <p>Results</p> <p><it>In vitro</it>, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. <it>In vivo</it>, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia.</p> <p>Conclusion</p> <p>Adrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug.</p

Stump closure reinforcement with absorbable fibrin collagen sealant sponge (TachoSil®) does not prevent pancreatic fistula after distal pancreatectomy: the FIABLE* multicenter controlled randomized study

International audienceBackground - The aim of this study is to evaluate the effectiveness of TachoSil sponge on distal pancreatectomy remnant stump in reducing the rate and severity of postoperative pancreatic fistula (POPF). Methods - All consecutive patients requiring distal pancreatectomy were randomized in 45 centers. The principal end point was onset of "clinically relevant" POPF. Univariate and multivariate analyses were searched for predictive factors. Results - Of the 270 patients randomized (134 with TachoSil; 136 without), 150 (55.6%) patients sustained a POPF [74 clinically relevant and 76 clinically silent (27.4% and 28.1%), respectively]: no statistically significant difference was found between patients sustaining clinically relevant POPF [41 (30.6%) with vs 33 (24.3%) without TachoSil (P = .276)], or overall POPF [73 (54.5%) with vs 77 (56.6%) without TachoSil, (P = .807)], but there were more clinically relevant POPF after hand-sewn (32.3%) versus mechanical closure (19.8%) (P = .025) and, in case of splenic preservation, after splenic vessel ligation (15/32, 46.9%) versus vascular preservation (17/72, 23.6%) (P = .024). Hand-sewn pancreatic remnant closure (P = .023) and splenic vessel ligation in splenic preservation (P = .035) were independent predictive factors for the onset of clinically relevant POPF. Conclusion - TachoSil sponge reinforcement of the proximal remnant after distal pancreatectomy reduced neither the rate nor the severity of POPF

Are there any differences in clinical and laboratory findings on admission between H1N1 positive and negative patients with flu-like symptoms?

<p>Abstract</p> <p>Background</p> <p>The World Health Organization alert for the H1N1 influenza pandemic led to the implementation of certain measures regarding admission of patients with flu-like symptoms. All these instructions were adopted by the Greek National Health System. The aim of this study was to retrospectively examine the characteristics of all subjects admitted to the Unit of Infectious Diseases with symptoms indicating H1N1 infection, and to identify any differences between H1N1 positive or negative patients. Patients from the ED (emergency department) with flu-like symptoms (sore throat, cough, rhinorhea, or nasal congestion) and fever >37.5°C were admitted in the Unit of Infectious diseases and gave pharyngeal or nasopharyngeal swabs. Swabs were tested with real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR).</p> <p>Findings</p> <p>Patients were divided into two groups. Group A comprised 33 H1N1 positive patients and Group B (control group) comprised of 27 H1N1 negative patients. The two groups did not differ in terms of patient age, co-morbidities, length of hospitalization, temperature elevation, hypoxemia, as well as renal and liver function. There were also no significant differences in severity on admission. C-reactive protein (CRP) (mean 12.8 vs. 5.74) and white blood count (WBC) (mean 10.528 vs. 7.114) were significantly higher in group B than in group A upon admission. Obesity was noted in 8 patients of Group A (mean 31.67) and 14 patients of Group B (mean 37.78). Body mass index (BMI) was lower in H1N1 positive than in H1N1 negative patients (mean 31.67 vs. 37.78, respectively; p = 0.009).</p> <p>Conclusions</p> <p>The majority of patients in both groups were young male adults. CRP, WBC and BMI were higher among H1N1 negative patients. Finally, clinical course of patients in both groups was mild and uneventful.</p

Splenic TFH expansion participates in B-cell differentiation and antiplatelet-antibody production during immune thrombocytopenia

Antiplatelet-antibody-producing B cells play a key role immune thrombocytopenia (ITP) pathogenesis; however, little is known about T-cell dysregulations that support B-cell differentiation. During the past decade, T follicular helper cells (TFHs) have been characterized as the main T-cell subset within secondary lymphoid organs that promotes B-cell differentiation leading to antibody class-switch recombination and secretion. Herein, we characterized TFHs within the spleen of 8 controls and 13 ITP patients. We show that human splenic TFHs are the main producers of interleukin (IL)-21, express CD40 ligand(CD154), and are located within the germinal center of secondary follicles. Compared with controls, splenic TFH frequency is higher in ITP patients and correlates with germinal center and plasma cell percentages that are also increased. In vitro, IL-21 stimulation combined with an anti-CD40 agonist antibody led to the differentiation of splenic B cells into plasma cells and to the secretion of antiplatelet antibodies in ITP patients. Overall, these results point out the involvement of TFH in ITP pathophysiology and the potential interest of IL-21 and CD40 as therapeutic targets in ITP

Trials

BACKGROUND: Postoperative upper gastrointestinal fistula (PUGIF) is a devastating complication, leading to high mortality (reaching up to 80%), increased length of hospital stay, reduced health-related quality of life and increased health costs. Nutritional support is a key component of therapy in such cases, which is related to the high prevalence of malnutrition. In the prophylactic setting, enteral nutrition (EN) is associated with a shorter hospital stay, a lower incidence of severe infectious complications, lower severity of complications and decreased cost compared to total parenteral nutrition (TPN) following major upper gastrointestinal (GI) surgery. There is little evidence available for the curative setting after fistula occurrence. We hypothesize that EN increases the 30-day fistula closure rate in PUGIF, allowing better health-related quality of life without increasing the morbidity or mortality. METHODS/DESIGN: The NUTRILEAK trial is a multicenter, randomized, parallel-group, open-label phase III trial to assess the efficacy of EN (the experimental group) compared with TPN (the control group) in patients with PUGIF. The primary objective of the study is to compare EN versus TPN in the treatment of PUGIF (after esophagogastric resection including bariatric surgery, duodenojejunal resection or pancreatic resection with digestive tract violation) in terms of the 30-day fistula closure rate. Secondary objectives are to evaluate the 6-month postrandomization fistula closure rate, time of first fistula closure (in days), the medical- and surgical treatment-related complication rate at 6 months after randomization, the fistula-related complication rate at 6 months after randomization, the type and severity of early (30 days after randomization) and late fistula-related complications (over 30 days after randomization), 30-day and 6-month postrandomization mortality rate, nutritional status at day 30, day 60, day 90 and day 180 postrandomization, the mean length of hospital stay, the patient's health-related quality of life (by self-assessment questionnaire), oral feeding time and direct costs of treatment. A total of 321 patients will be enrolled. DISCUSSION: The two nutritional supports are already used in daily practice, but most surgeons are reluctant to use the enteral route in case of PUGIF. This study will be the first randomized trial testing the role of EN versus TPN in PUGIF. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03742752. Registered on 14 November 2018.This research program is funded by the French Ministry of Health through Programme Hospitalier de Recherche Clinique 2016

Cómo disminuir la mortalidad de la fístula anastomótica en cirugía colorrectal?

Lettre à l'éditeur ("Cirugía Española" vol.94, n°4) http://www.elsevier.es/es-revista-cirugia-espanola-36-linkresolver-como-disminuir-mortalidad-fistula-anastomotica-S0009739X1500319

More about the "heterogeneity" of Merkel cell carcinoma.

International audienc

Quelle méthode utiliser pour réaliser la chimiothérapie hyperthermique intrapéritonéale dans le traitement des carcinoses péritonéales? (étude expérimentale comparative des techniques ouverte et fermée)

DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF

Perfusion de cisplatine hypotonique dans le foie isolé (étude de faisabilité et de tolérance chez le porc)

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF