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Abstract Background Opioid-free anesthesia (OFA) is associated with significantly reduced cumulative postoperative morphine consumption in comparison with opioid-based anesthesia (OBA). Whether OFA is feasible and may improve outcomes in pancreatic surgery remains unclear. Methods Perioperative data from 77 consecutive patients who underwent pancreatic resection were included and retrospectively reviewed. Patients received either an OBA with intraoperative remifentanil (n = 42) or an OFA (n = 35). OFA included a combination of continuous infusions of dexmedetomidine, lidocaine, and esketamine. In OBA, patients also received a single bolus of intrathecal morphine. All patients received intraoperative propofol, sevoflurane, dexamethasone, diclofenac, neuromuscular blockade. Postoperative pain management was achieved by continuous wound infiltration and patient-controlled morphine. The primary outcome was postoperative pain (Numerical Rating Scale, NRS). Opioid consumption within 48 h after extubation, length of stay, adverse events within 90 days, and 30-day mortality were included as secondary outcomes. Episodes of bradycardia and hypotension requiring rescue medication were considered as safety outcomes. Results Compared to OBA, NRS (3 [2–4] vs 0 [0–2], P

Simple Summary: Patients with pancreatic ductal adenocarcinoma (PDAC) are increasingly receiving neoadjuvant therapy (NAT) with the aim of improving patient care. However, complete tumor regression remains rare, and there is a dire need for biomarkers that can predict responses to NAT. SMAD4 is a protein that is inactivated in about half of PDACs and has been described as associated with metastasis and resistance to therapy. The aim of our study is to investigate whether SMAD4 status is a prognostic and predictive factor in patients with pancreatic cancer receiving NAT. In our cohort of patients, SMAD4 loss was associated with quicker progression and metastasis development. When patients were subgrouped depending on their type of neoadjuvant treatment, those receiving FOLFIRINOX-based NAT and presenting SMAD4-positive tumors showed the best outcome. This result suggests that SMAD4 may be a potential biomarker for patients with pancreatic cancer receiving NAT and may help improve patient care. Background: SMAD4 is inactivated in 50–55% of pancreatic ductal adenocarcinomas (PDACs). SMAD4 loss of expression has been described as a negative prognostic factor in PDAC associated with an increased rate of metastasis and resistance to therapy. However, the impact of SMAD4 inactivation in patients receiving neoadjuvant therapy (NAT) is not well characterized. The aim of our study was to investigate whether SMAD4 status is a prognostic and predictive factor in patients receiving NAT. Methods: We retrospectively analyzed 59 patients from a single center who underwent surgical resection for primary PDAC after NAT. SMAD4 nuclear expression was assessed by immunohistochemistry, and its relationship to clinicopathologic variables and survival parameters was evaluated. Interaction testing was performed between SMAD4 status and the type of NAT. Results: 49.15% of patients presented loss of SMAD4. SMAD4 loss was associated with a higher positive lymph node ratio (p = 0.03), shorter progression-free survival (PFS) (p = 0.02), and metastasis-free survival (MFS) (p = 0.02), but it was not an independent prognostic biomarker in multivariate analysis. Interaction tests demonstrated that patients with SMAD4-positive tumors receiving FOLFIRINOX-based NAT showed the best outcome. Conclusion: This study highlights the potential prognostic and predictive role of SMAD4 status in PDAC patients receiving FOLFIRINOX-based NAT. [ABSTRACT FROM AUTHOR]

Background: Our aim was to evaluate the feasibility and safety of isotoxic high-dose (iHD) stereotactic body radiation therapy (SBRT) in a total neoadjuvant sequence for the treatment of localized pancreatic adenocarcinoma. Materials and methods: Biopsy-proven borderline resectable/locally advanced pancreatic cancer (BR/LAPC) patients were included in this observational prospective analysis from August 2017 to April 2020 without excluding tumours showing a radiological direct gastrointestinal (GI) invasion. An induction chemotherapy by modified fluorouracil, irinotecan and oxaliplatin was performed for a median of six cycles. In case of non-progression, an isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) was delivered in 5 fractions followed by a surgical exploration. The primary endpoint was acute/late gastrointestinal grade ⩾3 toxicity. Secondary endpoints were overall survival (OS), progression-free survival (PFS) and local control (LC). Results: A total of 39 consecutive patients (21 BR and 18 LAPC) were included: 34 patients (87.2%, 18 BR and 16 LAPC) completed the planned neoadjuvant sequence. After iHD-SBRT, 19 patients [55.9% overall, 13/18 BR (72.2%) and 6/16 LAPC (37.5%)] underwent an oncological resection among the 25 patients surgically explored (73.5%). The median follow up was 18.2 months. The rates of acute and late GI grade 3 toxicity were, respectively, 2.9% and 4.2%. The median OS and PFS from diagnosis were, respectively, 24.5 and 15.6 months. The resected patients had improved median OS and PFS in comparison with the non-resected patients (OS: 32.3 versus 18.2 months, p = 0.02; PFS: 24.1 versus 7.1 months, p < 0.001). There was no survival difference between the BR and LAPC patients. The 1-year LC from SBRT was 74.1% and the median locoregional PFS was not reached for both BR and LAPC patients. Conclusions: iHD-SBRT displays an excellent toxicity profile, also for potentially high-risk patients with radiological direct GI invasion at diagnosis and can be easily integrated in a total neoadjuvant strategy. The oncological outcomes are promising and emphasise the need for further exploration of iHD-SBRT in phase II/III trials. [ABSTRACT FROM AUTHOR]

Background and study aims: Paraduodenal pancreatitis is histologically well defined but its epidemiology, natural history, and connection with chronic pancreatitis are not completely understood. The aim of this study was to review the endoscopic and medical management of paraduodenal pancreatitis. Patients and methods: Medical records of all patients with paraduodenal pancreatitis diagnosed by magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasonography (EUS) between 1995 and 2010 were retrospectively reviewed. Clinical features, imaging procedures, and treatments were investigated. The primary end point was the rate of clinical success, and the secondary end points were the radiological or endoscopic improvement, complication rate, and overall survival rate. Results: A total of 51 patients-were included in the study (88.2% alcohol abuse; median age 49 years [range 37-70]; 50 men). The most frequent symptoms at presentation were pain (n=50; 98.0 %) and weight loss (n=36; 70.6 %). Chronic pancreatitis was present in 36 patients (70.6 %), and 45 patients (88.2 %) had cysts. Other findings included stricture of the pancreatic duct (n=37; 72.5 %), common bile duct (n=29; 56.9 %), and duodenum (n=24; 47.1 %). A total of 39 patients underwent initial endoscopic treatment: cystenterostomy (n=20), pancreatic and/or biliary duct drainage (n=19), and/or duodenal dilation (n= 6). For the patients with available follow-up (n= 41), 24 patients required repeat endoscopy and 9 patients required surgery after the initial endoscopic management. After a median follow-up of 54 months (range 6-156 months), complete clinical success was achieved in 70.7% of patients, and the overall survival rate was 94.1 %. Conclusions: This is the largest series concerning the management of paraduodenal pancreatitis using endotherapy as the first-line intervention. Although repeat endoscopic procedures were required in half of the patients, no severe complication was observed and surgical treatment was ultimately needed in less than 25% of the patients. [ABSTRACT FROM AUTHOR]

The article presents a case study of 41-year-old man with a 24-hour history of melena and exacerbated epigastric pain six years after undergoing a laparoscopic Roux-en-Y gastric bypass for morbid obesity. The patient underwent a laparotomy, which revealed an internal hernia in the Petersen space. The article also discusses the causes of digestive bleeding related to a chronic splanchnic vascular stricture.

Background: Sleeve gastrectomy (SG) is the most frequently performed bariatric procedure in the world. Our purpose was to evaluate the percentage of excess weight loss (%EWL), resolution of obesity-related comorbidities after SG, and identify predictive factors of weight loss failure.Methods: A prospective cohort study of adults who underwent SG during 2014 in 7 Belgian-French centers. Their demographic, preoperative, and postoperative data were prospectively collected and analyzed statistically.Results: Overall, 529 patients underwent SG, with a mean preoperative weight and body mass index (BMI) of 118.9 ± 19.9 kg and 42.9 ± 5.5 kg/m2, respectively. Body mass index significantly decreased to 32.2 kg/m2 at 5 years (P < .001). The mean %EWL was 63.6% at 5 years. A significant reduction in dyslipidemia (28.0%-18.2%), obstructive sleep apnea (OSAS) (34.6%-25.1%), and arterial hypertension (HTN) (30.4%-21.5%) was observed after 5 years, but not for diabetes and gastroesophageal reflux disease (GERD). At multivariate analysis, age >50 years old, BMI >50 kg/m2, and previous laparoscopic adjustable gastric banding (LAGB) remained independent predictors of weight loss failure.Conclusions: Five years after SG, weight loss was satisfactory; the reduction of comorbidities was significant for dyslipidemia, OSAS, and HTN, but not diabetes and GERD. Age >50 years old, BMI >50 kg/m2, and previous LAGB were independent predictors of weight loss failure. [ABSTRACT FROM AUTHOR]

Background/aims: In 2006, a TNM system for foregut neuroendocrine tumors has been proposed. Our study aimed to present the management of neuroendocrine tumors of pancreas according to this classification and to highlight some of its limitations., Methodology: Clinical, biochemical, radiological, surgical and pathological data were retrospectively collected on 22 consecutives patients, who underwent surgery for neuroendocrine tumors of pancreas between November, 1991 and September, 2005. These data were used to set the TNM., Results: After excluding 5 patients, the remaining 17 patients were analyzed. In 9 patients, with a mean age of 39 years, tumors were benign with a mean size of 1.8 cm, classed at stage I-IIa, whereas for 8 patients with a mean age of 57 years, tumors were malignant with a mean size of 6cm and were classed at stage IIb-IV. There were 3 deaths in stage IIb-IV, and none in stage I-IIa., Conclusion: TNM may be considered as a useful tool for prognostic stratification, but true benign tumors need to be excluded in order to improve the classification. Size and age appeared as variables affecting malignant behavior and the prognosis.

Tolerance to African trypanosomes requires the production of IFN-gamma in the early stage of infection that triggers the development of classically activated macrophages controlling parasite growth. However, once the first peak of parasitemia has been controlled, down-regulation of the type 1 immune response has been described. In this study, we have evaluated whether regulatory T cells (Tregs) contribute to the limitation of the immune response occurring during Trypanosoma congolense infection and hereby influence the outcome of the disease in trypanotolerant C57BL/6 host. Our data show that Foxp3+ Tregs originating from the naturally occurring Treg pool expanded in the spleen and the liver of infected mice. These cells produced IL-10 and limited the production of IFN-gamma by CD4+ and CD8+ effector T cells. Tregs also down-regulated classical activation of macrophages resulting in reduced TNF-alpha production. The Treg-mediated suppression of the type 1 inflammatory immune response did not hamper parasite clearance, but was beneficial for the host survival by limiting the tissue damages, including liver injury. Collectively, these data suggest a cardinal role for naturally occurring Tregs in the development of a trypanotolerant phenotype during African trypanosomiasis.

Kidney ischemia/reperfusion injury (I/R) is characterized by renal dysfunction and tubular damages resulting from an early activation of innate immunity. Recently, nicotine administration has been shown to be a powerful inhibitor of a variety of innate immune responses, including LPS-induced toxaemia. This cholinergic anti-inflammatory pathway acts via the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). Herein, we tested the potential protective effect of nicotine administration in a mouse model of renal I/R injury induced by bilateral clamping of kidney arteries. Renal function, tubular damages and inflammatory response were compared between control animals and mice receiving nicotine at the time of ischemia. Nicotine pretreatment protected mice from renal dysfunction in a dose-dependent manner and through the alpha7nAChR, as attested by the absence of protection in alpha7nAChR-deficient mice. Additionally, nicotine significantly reduced tubular damages, prevented neutrophil infiltration and decreased productions of the CXC-chemokine KC, TNF-alpha and the proinflammatory high-mobility group box 1 protein. Reduced tubular damage in nicotine pre-treated mice was associated with a decrease in tubular cell apoptosis and proliferative response as attested by the reduction of caspase-3 and Ki67 positive cells, respectively. All together, these data highlight that nicotine exerts a protective anti-inflammatory effect during kidney I/R through the cholinergic alpha7nAChR pathway. In addition, this could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation.