Surgical management of abdominal and retroperitoneal Castleman's disease

BACKGROUND: Abdominal and retroperitoneal Castleman's disease could present either as a localized disease or as a systemic disease. Castleman's disease is a lymphoid hyperplasia related to human Herpes virus type 8, which could have an aggressive behavior, similar to that of malignant lymphoid neoplasm mainly with the systemic type, or a benign one in its localized form. METHODS: The authors report two cases of localized Castleman's disease in the retroperitoneal space and review the current and recent progress in the knowledge of this atypical disease. CASES PRESENTATION: The two patients were young healthy women presenting with a hyper vascular peri-renal mass suggestive of malignant tumor. Both have been resected in-toto. One of them had an extensive resection with nephrectomy, while the second had a kidney preserving surgery. Pathological examination revealed localized Castleman's disease and surgical margins were free of disease. Postoperative course was uneventful, and after more than 5-years of follow-up no recurrences have been observed. CONCLUSION: Localized Castleman's disease should be considered when facing a solid hypervascular abdominal or retroperitoneal mass. A better knowledge of this disorder and its characteristic would help surgeon to avoid unnecessarily extensive resection for this benign disorder when dealing with abdominal or retroperitoneal tumors. Surgical resection is curative for the localized form, when complete, while splenectomy could be indicated for the systemic form

Reducing Cost of Surgery by Avoiding Complications: the Model of Robotic Roux-en-Y Gastric Bypass

Background: Robotic surgery is a complex technology offering technical advantages over conventional methods. Still, clinical outcomes and financial issues have been subjects of debate. Several studies have demonstrated higher costs for robotic surgery when compared to laparoscopy or open surgery. However, other studies showed fewer costly anastomotic complications after robotic Roux-en-Y gastric bypass (RYGBP) when compared to laparoscopy. Methods: We collected data for our gastric bypass patients who underwent open, laparoscopic, or robotic surgery from June 1997 to July 2010. Demographic data, BMI, complications, mortality, intensive care unit stay, hospitalization, and operating room (OR) costs were analyzed and a cost projection completed. Sensitivity analyses were performed for varied leak rates during laparoscopy, number of robotic cases per month, number of additional staplers during robotic surgery, and varied OR times for robotic cases. Results: Nine-hundred ninety patients underwent gastric bypass surgery at the University Hospital Geneva from June 1997 to July 2010. There were 524 open, 323 laparoscopic, and 143 robotic cases. Significantly fewer anastomotic complications occurred after open and robotic RYGBP when compared to laparoscopy. OR material costs were slightly less for robotic surgery (USD 5,427) than for laparoscopy (USD 5,494), but more than for the open procedure (USD 2,251). Overall, robotic gastric bypass (USD 19,363) was cheaper when compared to laparoscopy (USD 21,697) and open surgery (USD 23,000). Conclusions: Robotic RYGBP can be cost effective due to balancing greater robotic overhead costs with the savings associated with avoiding stapler use and costly anastomotic complication

Learning curve for robot-assisted Roux-en-Y gastric bypass

Background: Robot-assisted Roux-en-Y gastric bypass (RYGBP) is rapidly evolving as an important surgical approach in the bariatric field. However, the specific learning curve associated with this new approach remains poorly investigated. This study aimed to evaluate the learning curve for robot-assisted RYGBP. Methods: A series of 64 consecutive robot-assisted RYGBP procedures were performed between December 2008 and December 2010 by a single surgeon already experienced in advanced laparoscopic procedures but not in bariatric surgery. All data were collected prospectively in a database and reviewed retrospectively. The learning curve was evaluated using the cumulative sum (CUSUM) method. Results: Women comprised 76.6% and men 23.4% of this series. These patients had a mean age of 43years and a mean body mass index (BMI) of 44.5kg/m2. The mean operative time (OT) was 238.1min (range, 150-400min). A total of six complications occurred (9.4%). The CUSUM learning curve consisted of two distinct phases: phase 1 (the initial 14 cases; mean OT, 288.9min) and phase 2 (the subsequent cases; mean OT, 223.6min), which represented the mastery phase, with a decrease in OT (P=0.0001). The two groups were similar in terms of gender, age, and BMI. The two phases did not differ in terms of complications or hospital stay. Conclusions: This series confirms previous study findings concerning the feasibility and the safety of robotic RYGBP even after a limited experience with laparoscopic RYGBP. The data reported in this article suggest that the learning phase for robot-assisted RYGBP can be achieved with 14 case

Robot-Assisted Roux-en-Y Gastric Bypass for Super Obese Patients: A Comparative Study

Superobese patients (SO) (body mass index (BMI) ≥ 50kg/m2) represent a real surgical challenge and the best management remains debatable. While the safety of a laparoscopic approach has been questioned for this population, robotics has been introduced in the armamentarium of the bariatric surgeon, yet its role remains poorly assessed, especially for a very high BMI. The study aim is thus to report our experience with robot-assisted Roux-en-Y gastric bypass (RYGB) for SO. From July 2006 to May 2012, 288 consecutive robot-assisted RYGB procedures have been performed at a single institution. All data were collected prospectively in a dedicated database. Among those patients, 41 were SO (14.2%). All the peri- and postoperative parameters were compared to the morbidly obese (MO) group (BMI < 50). Data have been reviewed retrospectively. The SO group presented a higher ASA score and more male patients. The operative time was similar between both groups, yet there were more conversions in the SO group (two versus one for MO; p = 0.05). The morbidity and mortality rates were similar between both groups. The length of stay was longer for the SO population (7 vs. 6days; p = 0.03). The percent BMI loss was similar at 1year (34 vs. 34%; p = 1), but the percent excess BMI loss was higher for the MO group (83 vs. 65% for the SO group; p = 0.0007). Robot-assisted RYGB can be performed safely for SO, with complication rates and functional results at 1year comparable to MO, yet this approach for SO has been associated with a slightly increased conversion rate and length of sta

Laparoscopic Versus Robotic Roux-En-Y Gastric Bypass: Lessons and Long-Term Follow-Up Learned From a Large Prospective Monocentric Study

Background: Laparoscopic Roux-en-Y gastric bypass (RYGB) has become the procedure of choice for the treatment of morbid obesity. Recently, several reports have shown the potential advantages of the robotic approach, notably by reducing complications. The aim of this study is to report our long-term experience with robotic Roux-en-Y gastric bypass (RYGB) and to compare outcomes with the laparoscopic approach. Methods: From January 2003 to September 2013, 777 consecutive minimally invasive RYGB have been performed in our institution: 389 laparoscopically (50.1%) and 388 robotically (49.9%). During the study period, all the data regarding these consecutive RYGB has been prospectively collected in a dedicated database. Results: While longer in duration compared to laparoscopy (+30min; p = 0.0001), the robotic approach had a lower conversion rate (0.8 vs. 4.9%; p = 0.0007), and less complications (11.6% vs. 16.7%; p = 0.05), in particular, less gastrointestinal leaks (0.3 vs. 3.6%; p = 0.0009). There were also less early reoperations (1 vs. 3.3%; p = 0.05) and a shorter hospital stay in the robotic group (6.2 vs. 10.4days; p = 0.0001). There were no statistical differences between the early and the current robotic experience, except in operative time and hospital stay, which were shorter for the last 100 cases. Finally, the BMI loss was significantly higher in the laparoscopic group starting at the first post-operative year. Conclusions: Robotic RYGB is not only safe and feasible, but also a valid option in comparison to laparoscopy. At the cost of a longer operative time, we observed better short-term outcomes with the robotic approach

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Régulation de la prolifération cellulaire au cours de la cicatrisation cutanée (rôle de p27KIP1, un inhibiteur des Kinases Dépendantes des Cyclines)

La cicatrisation cutanée consiste en un programme dynamique et coordonné d'événements, dont les signaux initiateurs conduisent des cellules quiescentes, situées aux berges de la blessure, à migrer, proliférer et déposer une nouvelle matrice dans le lit de la blessure, de manière à restaurer à la peau son intégrité physique et fonctionnelle. La prolifération, en particulier celle des fibroblastes dermiques, est une étape essentielle de ce processus. Des pathologies cicatricielles comme les chéloïdes, les cicatrices hypertrophiques et les ulcères sont des exemples de désordres fibroprolifératifs et il est actuellement admis que la chronicité du processus de cicatrisation contribue à l'apparition de certains carcinomes spinocellulaires. Si la cicatrisation est bien étudiée d'un point de vue descriptif, il n'existe en revanche aucun système biologique performant permettant une étude moléculaire. Pour contourner cette difficulté, nous avons développé un système original et reproductible qui mime in vitro les différentes étapes du processus et permet la détection et la quantification des événements moléculaires associés. Mon travail de thèse a eu pour but de comprendre les mécanismes moléculaires à l'origine 1) de l'entrée des fibroblastes dermiques dans le cycle cellulaire en réponse à une blessure, et 2) de leur arrêt de prolifération une fois la blessure refermée. Nous décrivons pour la première fois que la blessure mécanique d'un tapis confluent de fibroblastes provoque une entrée synchrone des cellules dans le cycle cellulaire. Cette entrée en cycle s'accompagne d'une diminution de l'ARN messager de p27, un inhibiteur de l'activité des cyclines-dépendantes kinases qui joue un rôle clef dans le contrôle de la prolifération cellulaire, et de la stimulation de l'expression d'Id3, un gène de réponse précoce codant un inhibiteur de l'activité transcriptionnelle des facteurs de type bHLH. Grâce à une approche siRNA, nous démontrons qu'Id3 contrôle la diminution de p27, permettant l'entrée en cycle et la division cellulaire. Lorsque la lésion est comblée, la prolifération cellulaire s'arrête et les cellules entrent dans une nouvelle phase de quiescence. Nous avons démontré que cette sortie de cycle est précédée i) d'une stabilisation pré-mitotique de l'inhibiteur p27, ii) de son association avec les complexes cycline A-Cdk1/2 et cycline D1-Cdk4/6, iii) d'une diminution de la phosphorylation des " pocket " protéines pRb et p130. En revanche, p27 ne s'associe pas avec les complexes cycline B1-Cdk1 et n'inhibe pas leur activité enzymatique. Les fibroblastes dermiques entrent donc en mitose puis sortent du cycle de manière réversible dans la phase G1 suivante. La réduction du niveau d'expression de p27 par une approche siRNA réverse partiellement ce phénotype. En conclusion, notre travail démontre pour la première fois dans le contexte physiologique de la cicatrisation cutanée, que p27 est l'élément clef qui contrôle à la fois l'entrée des cellules en cycle et leur sortie en fin de cicatrisation, et qu'il est un médiateur de signaux antiprolifératifs agissant après le point de restriction et avant la mitose.Skin wound healing is a complex phenomenon that involves multiple cellular processes (migration, proliferation, differenciation...) and cell types allowing the reconstruction of skin lesions. Many genetic or acquired defects can perturb the normal wound healing process, leading to skin pathologies like hypertrophic scars, keloïds or ulcers, in which fibroblasts are characterised by an abnormal proliferation. However, the molecular abnormalities at the origin of these pathologies are still unknown notably because the classical experimental systems do not allow a molecular approach of the process. To circumvent this hurdle, we have developed an original device that performs calibrated injuries and enables the detection of a wide range of molecular events activated during wound healing. Using this experimental system, we show that mechanical lesions performed within confluent human dermal fibroblasts provoke a synchronous cell cycle entry followed by a cell cycle exit after mitosis. We demonstrate that the mRNA of p27Kip1, a cyclin-dependent kinase (Cdk) inhibitor which plays a key role in negative control of cell proliferation, is transiently downregulated after injury. We identify Id3, a bHLH transcriptional repressor, as a candidate for p27 down regulation. Id3-siRNA reversed the injury mediated p27 down-regulation and blocks the cell cycle progression, demonstrating that Id3 is involved in the transcriptional repression of p27 and that this early regulation is required for cell proliferation. When cells reach confluence, the cell cycle exit is preceded by pre-mitotic stabilization of p27 and association with cyclin A-Cdk1/2 and cyclin D1-Cdk4/6 (but not cyclin B1-Cdk1) complexes, and decreased pocket protein phosphorylation. Reduction of p27 by siRNA partially reverses this phenotype, supporting a role for p27 as a mediator of anti-proliferative cues occurring after the restriction point.NICE-BU Sciences (060882101) / SudocPARIS-Académie Médecine (751065201) / SudocSudocFranceF

The role of revascularization in celiac occlusion and pancreatoduodenectomy

Performance of pancreatoduodenectomy involves sacrifice of the gastroduodenal artery (GDA), which poses an ischemic threat to the liver, stomach, pancreas, and various anastomoses in patients with celiac trunk occlusion