58 research outputs found
Silencing mutated β-catenin inhibits cell proliferation and stimulates apoptosis in the adrenocortical cancer cell line H295R
Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine neoplasm, with limited therapeutic options. Activating β-catenin somatic mutations are found in ACC and have been associated with a poor clinical outcome. In fact, activation of the Wnt/β-catenin signaling pathway seems to play a major role in ACC aggressiveness, and might, thus, represent a promising therapeutic target.
Similar to patient tumor specimen the H295 cell line derived from an ACC harbors a natural activating β-catenin mutation. We herein assess the in vitro and in vivo effect of β-catenin inactivation using a doxycyclin (dox) inducible shRNA plasmid in H295R adrenocortical cancer cells line (clone named shβ).
Following dox treatment a profound reduction in β-catenin expression was detectable in shβ clones in comparison to control clones (Ctr). Accordingly, we observed a decrease in Wnt/βcatenin-dependent luciferase reporter activity as well as a decreased expression of AXIN2 representing an endogenous β-catenin target gene. Concomitantly, β-catenin silencing resulted in a decreased cell proliferation, cell cycle alterations with cell accumulation in the G1 phase and increased apoptosis in vitro. In vivo, on established tumor xenografts in athymic nude mice, 9 days of β-catenin silencing resulted in a significant reduction of CTNNB1 and AXIN2 expression. Moreover, continous β-catenin silencing, starting 3 days after tumor cell inoculation, was associated with a complete absence of tumor growth in the shβ group while tumors were present in all animals of the control group.
In summary, these experiments provide evidences that Wnt/β-catenin pathway inhibition in ACC is a promising therapeutic target
Study Protocol of the ESAP Study: Endoscopic Papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodenectomy for Ampullary Neoplasm—A Pancreas2000/EPC Study
Background: Lesions of the Ampulla of Vater are a rare condition and represent <10%
of peri-ampullary neoplasms. Nevertheless, ampullary adenomas have the potential
for malignant transformation to ampullary carcinomas by an adenoma-to-carcinoma
sequence. Thus, adequate patient selection and complete resection (R0) of non-invasive
ampullary lesions either by endoscopic papillectomy (EP), surgical ampullectomy (SA),
or pancreaticoduodenectomy (PD) is essential. Although PD was traditionally performed,
recent studies reported considerable efficacy and fewer complications following EP and
SA. Since consistent comparative data are lacking, the Endoscopic Papillectomy vs.
Surgical Ampullectomy vs. Pancreaticoduodectomy (ESAP) study will provide evidence
for a therapeutic standard and post procedure morbidity in ampullary lesions.
Methods: International multicenter retrospective study. Adult patients (>18 years of
age) who underwent SA or PD for ampullary neoplasm between 2004 and 2018 or
EP between 2007 and 2018 will be evaluated. Main inclusion criteria are ampullary
lesions strictly located to the ampulla. This includes adenoma, adenocarcinoma (T1 and
T2), neuroendocrine tumors, gastrointestinal stroma tumors and other rare conditions.
Exclusion criteria are peri-ampullary lesions, e.g., from the duodenal wall or the head
of the pancreas, and interventions for tumor stages higher than T2. The main objective
of this study is to analyze rates of complete resection (R0), recurrence and necessity
for complementary interventions following EP, SA, and PD. Treatment-quality for each
procedure will be defined by morbidity, mortality and complication rates and will be
compared between EP, SA, and PD. Secondary objectives include outcome for patients
with incomplete resection or initially understated tumors, lesions of the minor papilla,
hereditary syndromes, neuroendocrine tumors, mesenchymal lesions, and other rare
conditions. Additionally, we will analyze therapy by argon plasma coagulation and
radiofrequency ablation. Furthermore, outcome in curative and palliative interventions
can be distinguished.
Conclusion: The ESAP study will provide evidence for therapeutic algorithms and
data for the implementation of guidelines in the treatment of different types of ampullary
tumors, including recurrent, or incomplete resected lesions
Systematic Review with Meta-Analysis: Endoscopic and Surgical Resection for Ampullary Lesions
Ampullary lesions (ALs) can be treated by endoscopic (EA) or surgical ampullectomy (SA) or pancreaticoduodenectomy (PD). However, EA carries significant risk of incomplete resection while surgical interventions can lead to substantial morbidity. We performed a systematic review and meta-analysis for R0, adverse-events (AEs) and recurrence between EA, SA and PD. Electronic databases were searched from 1990 to 2018. Outcomes were calculated as pooled means using fixed and random-effects models and the Freeman-Tukey-Double-Arcsine-Proportion-model. We identified 59 independent studies. The pooled R0 rate was 76.6% (71.8–81.4%, I2 = 91.38%) for EA, 96.4% (93.6–99.2%, I2 = 37.8%) for SA and 98.9% (98.0–99.7%, I2 = 0%) for PD. AEs were 24.7% (19.8–29.6%, I2 = 86.4%), 28.3% (19.0–37.7%, I2 = 76.8%) and 44.7% (37.9–51.4%, I2 = 0%), respectively. Recurrences were registered in 13.0% (10.2–15.6%, I2 = 91.3%), 9.4% (4.8–14%, I2 = 57.3%) and 14.2% (9.5–18.9%, I2 = 0%). Differences between proportions were significant in R0 for EA compared to SA (p = 0.007) and PD (p = 0.022). AEs were statistically different only between EA and PD (p = 0.049) and recurrence showed no significance for EA/SA or EA/PD. Our data indicate an increased rate of complete resection in surgical interventions accompanied with a higher risk of complications. However, studies showed various sources of bias, limited quality of data and a significant heterogeneity, particularly in EA studies
Une courte antibiothérapie diminue la fréquence des complications infectieuses après duodenopancréatectomie céphalique sur bile contaminée
PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF
The role of radiotherapy in locally advanced pancreatic cancer
International audienceAt diagnosis, about 15% of patients with pancreatic cancer present with a resectable tumour, 50% have a metastatic tumour, and 35% a locally advanced tumour, non-metastatic but unresectable due to vascular invasion, or borderline resectable. Despite the technical progress made in the field of radiation therapy and the improvement of the efficacy of chemotherapy, the prognosis of these patients remains very poor. Recently, the role of radiation therapy in the management of pancreatic cancer has been much debated. This review aims to evaluate the role of radiation therapy for patients with locally advanced tumours
Study Protocol of the ESAP Study: Endoscopic Papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodenectomy for Ampullary Neoplasm—A Pancreas2000/EPC Study
Background: Lesions of the Ampulla of Vater are a rare condition and represent <10%
of peri-ampullary neoplasms. Nevertheless, ampullary adenomas have the potential
for malignant transformation to ampullary carcinomas by an adenoma-to-carcinoma
sequence. Thus, adequate patient selection and complete resection (R0) of non-invasive
ampullary lesions either by endoscopic papillectomy (EP), surgical ampullectomy (SA),
or pancreaticoduodenectomy (PD) is essential. Although PD was traditionally performed,
recent studies reported considerable efficacy and fewer complications following EP and
SA. Since consistent comparative data are lacking, the Endoscopic Papillectomy vs.
Surgical Ampullectomy vs. Pancreaticoduodectomy (ESAP) study will provide evidence
for a therapeutic standard and post procedure morbidity in ampullary lesions.
Methods: International multicenter retrospective study. Adult patients (>18 years of
age) who underwent SA or PD for ampullary neoplasm between 2004 and 2018 or
EP between 2007 and 2018 will be evaluated. Main inclusion criteria are ampullary
lesions strictly located to the ampulla. This includes adenoma, adenocarcinoma (T1 and
T2), neuroendocrine tumors, gastrointestinal stroma tumors and other rare conditions.
Exclusion criteria are peri-ampullary lesions, e.g., from the duodenal wall or the head
of the pancreas, and interventions for tumor stages higher than T2. The main objective
of this study is to analyze rates of complete resection (R0), recurrence and necessity
for complementary interventions following EP, SA, and PD. Treatment-quality for each
procedure will be defined by morbidity, mortality and complication rates and will be
compared between EP, SA, and PD. Secondary objectives include outcome for patients
with incomplete resection or initially understated tumors, lesions of the minor papilla,
hereditary syndromes, neuroendocrine tumors, mesenchymal lesions, and other rare
conditions. Additionally, we will analyze therapy by argon plasma coagulation and
radiofrequency ablation. Furthermore, outcome in curative and palliative interventions
can be distinguished.
Conclusion: The ESAP study will provide evidence for therapeutic algorithms and
data for the implementation of guidelines in the treatment of different types of ampullary
tumors, including recurrent, or incomplete resected lesions
Impact of Oral Immunonutrition on Postoperative Morbidity in Digestive Oncologic Surgery
International audienceObjective: The objective of the present study was to assess the effect of preoperative immunonutrition on a nationwide scale.Background: According to international guidelines, immunonutrition should be prescribed before major oncologic digestive surgery to decrease postoperative morbidity. Nevertheless, this practice remains controversial.Methods: We used a prospective national health database named “Echantillon généraliste des Bénéficiaires.” Patients were selected with ICD10 codes of cancer and digestive surgery procedures from 2012 to 2016. Two groups were identified: with reimbursement of immunonutrition 45 days before surgery (IN-group) or not (no-IN-group). Primary outcome was 90-day severe morbidity. Secondary outcomes were postoperative length of stay (LOS) and overall survival. Logistic regression and survival analysis adjusted with IPW method were performed.Results: One thousand seven hundred seventy-one patients were included. The proportion of different cancers was as follows: 72% patients were included in the colorectal group, 14% in the hepato-pancreato-biliary group, and 12% in the upper gastrointestinal group. Patients from the IN-group (n = 606, 34%) were younger (67.1 ± 11.8 vs 69.2 ± 12.2 years, P < 0.001), with increased use of other oral nutritional supplements (49.5% vs 31.8%, P < 0.001) and had more digestive anastomoses (89.4% vs 83.0%, P < 0.001). There was no significant difference between the 2 groups for 90-day severe morbidity [odds ratio (OR): 0.91, 95% confidence interval (95% CI): 0.73–1.14] or in survival (hazard ratio: 0.89, 95% CI: 0.73–1.08). LOS were shorter in the IN-group [−1.26 days, 95% CI: −2.40 to −0.10)].Conclusion: The preoperative use of immunonutrition before major oncologic digestive surgery was not associated with any significant difference in morbidity or mortality. However, the LOS was significantly shorter in the IN-group
Study Protocol of the ESAP Study: Endoscopic Papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodenectomy for Ampullary Neoplasm—A Pancreas2000/EPC Study
Background: Lesions of the Ampulla of Vater are a rare condition and represent <10%
of peri-ampullary neoplasms. Nevertheless, ampullary adenomas have the potential
for malignant transformation to ampullary carcinomas by an adenoma-to-carcinoma
sequence. Thus, adequate patient selection and complete resection (R0) of non-invasive
ampullary lesions either by endoscopic papillectomy (EP), surgical ampullectomy (SA),
or pancreaticoduodenectomy (PD) is essential. Although PD was traditionally performed,
recent studies reported considerable efficacy and fewer complications following EP and
SA. Since consistent comparative data are lacking, the Endoscopic Papillectomy vs.
Surgical Ampullectomy vs. Pancreaticoduodectomy (ESAP) study will provide evidence
for a therapeutic standard and post procedure morbidity in ampullary lesions.
Methods: International multicenter retrospective study. Adult patients (>18 years of
age) who underwent SA or PD for ampullary neoplasm between 2004 and 2018 or
EP between 2007 and 2018 will be evaluated. Main inclusion criteria are ampullary
lesions strictly located to the ampulla. This includes adenoma, adenocarcinoma (T1 and
T2), neuroendocrine tumors, gastrointestinal stroma tumors and other rare conditions.
Exclusion criteria are peri-ampullary lesions, e.g., from the duodenal wall or the head
of the pancreas, and interventions for tumor stages higher than T2. The main objective
of this study is to analyze rates of complete resection (R0), recurrence and necessity
for complementary interventions following EP, SA, and PD. Treatment-quality for each
procedure will be defined by morbidity, mortality and complication rates and will be
compared between EP, SA, and PD. Secondary objectives include outcome for patients
with incomplete resection or initially understated tumors, lesions of the minor papilla,
hereditary syndromes, neuroendocrine tumors, mesenchymal lesions, and other rare
conditions. Additionally, we will analyze therapy by argon plasma coagulation and
radiofrequency ablation. Furthermore, outcome in curative and palliative interventions
can be distinguished.
Conclusion: The ESAP study will provide evidence for therapeutic algorithms and
data for the implementation of guidelines in the treatment of different types of ampullary
tumors, including recurrent, or incomplete resected lesions
Trichobezoar: A rare cause of bowel obstruction
A bezoar is an intraluminal mass formed by the accumulation of undigested material in the gastrointestinal tract. A trichobezoar is a bezoar made up of hair and is a rare cause of bowel obstruction of the proximal gastrointestinal tract. They are seen mostly in young women with trichotillomania and trichotillophagia and symptoms include epigastric pain, nausea, loss of appetite and bowel or gastric outlet obstruction. We herein describe a case of a trichobezoar that presented as a gastric outlet obstruction and was subsequently successfully removed via a laparotomy
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