Benign multicystic peritoneal mesothelioma in a sexagenerian man: an uncommon case presentation.

BACKGROUND: Multicystic mesothelial cyst is a rare, and usually benign, tumor which is rarely diagnosed preoperatively due to the poor specificity of its symptomatology. METHODS: We report the case of a 63-year-old man with multiple comorbidities (e.g. cryptogenic cirrhosis, chronic heart failure) and a history of surgical resection of a giant abdominal cyst, who complained of recurrent intermittent abdominal pain and vomiting that appeared several weeks before. Abdominal computed tomodensitometry (CT) revealed multiple diffusely localized cysts in the abdominal cavity, ranging from 30 mm to 210 mm. RESULTS: The patient underwent surgical resection of twelve intra-abdominal cysts, identified at final pathology as benign mesothelial cysts, which were probably a recurrence following the previous surgery for a single intra-abdominal cyst. Three months later, the patient recurred with development of two new intraperitoneal cysts, with an increasing volume on CT at last follow-up (18 months). Surveillance was recommended given the patient's comorbidities and the absence of symptoms. CONCLUSIONS: Surgical resection is the treatment of choice for multicystic peritoneal mesothelioma, a rare disease that should be considered more as a borderline tumor than a benign tumor, given the high risk of recurrence and possible malignant transformation.

Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma or a Metaphor for Heterogeneity: From Single-Cell Analysis to Whole-Body Imaging.

Pancreatic ductal adenocarcinoma (PDAC) represents a formidable challenge due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) in PDAC, characterized by intense stromal desmoplastic reactions and a dominant presence of cancer-associated fibroblasts (CAFs), significantly contributes to therapeutic resistance. However, within the heterogeneous CAF population, fibroblast activation protein (FAP) emerges as a promising target for Gallium-68 FAP inhibitor positron emission tomography (Ga68FAPI-PET) imaging. Notably, 68Ga-FAPI-PET demonstrates promising diagnostic sensitivity and specificity, especially in conjunction with low tracer uptake in non-tumoral tissues. Moreover, it provides valuable insights into tumor-stroma interactions, a critical aspect of PDAC tumorigenesis not adequately visualized through conventional methods. The clinical implications of this innovative imaging modality extend to its potential to reshape treatment strategies by offering a deeper understanding of the dynamic TME. However, while the potential of 68Ga-FAPI-PET is evident, ongoing correlative studies are essential to elucidate the full spectrum of CAF heterogeneity and to validate its impact on PDAC management. This article provides a comprehensive review of CAF heterogeneity in PDAC and explores the potential impact of 68Ga-FAPI-PET on disease management.

The impact of a multidisciplinary team approach on the management of focal pancreatic lesions: a single tertiary center experience.

Background: Multidisciplinary team (MDT) meetings aim to optimize patient management. We evaluated the impact of MDT discussions on the management and diagnosis of focal pancreatic lesions in a single tertiary center. Methods: All patients with an initial diagnosis of solid or cystic pancreatic lesion discussed in our institution's MDT meeting on pancreatic diseases between January 1, 2020, and December 31, 2021, were included. The impact of MDT discussion on patient management, defined as a modification of the initially proposed therapeutic plan after MDT discussion, as well as the criteria leading to this modification, were the primary outcomes. Impact on diagnosis was the secondary outcome. Results: A total of 522 patients were included. Of these, 185 (35.4%) and 337 (64.6%) had an initial diagnosis of cystic or solid lesion, respectively. The most common referral query was regarding the management plan (349/522; 66.9%). Endoscopy was the procedure most often proposed before MDT discussion (109/522; 20.9%). Overall, the MDT discussion led to modification of the management plan in 377/522 patients (72.2%), with a statistically significant difference between cystic and solid lesions (63.2% vs. 77.2%; P<0.001). Management modifications were mainly driven by revision of cross-sectional radiological images. MDT discussion led to modification of the diagnosis in 92/522 patients (17.6%), with a significant difference regarding cystic lesions (35.7% vs. 7.7%; P<0.001). Conclusion: MDT discussion impacts the management of patients with cystic and solid pancreatic lesions, leading to a modification of the initially proposed management in two-thirds of them, mainly through revision of cross-sectional imaging.

Preoperative treatment with mFOLFIRINOX or Gemcitabine/Nab-paclitaxel +/- isotoxic high-dose stereotactic body Radiation Therapy (iHD-SBRT) for borderline resectable pancreatic adenocarcinoma (the STEREOPAC trial): study protocol for a randomised comparative multicenter phase II trial.

BACKGROUND: For patients with pancreatic ductal adenocarcinoma (PDAC), surgical resection remains the only potentially curative treatment. Surgery is generally followed by postoperative chemotherapy associated with improved survival, yet neoadjuvant therapy is a rapidly emerging concept requiring to be explored and validated in terms of treatment options and oncological outcomes. In this context, stereotactic body radiation (SBRT) appears feasible and can be safely integrated into a neoadjuvant chemotherapy regimen of modified FOLFIRINOX (mFFX) with promising benefits in terms of R0 resection, local control and survival. However, the optimal therapeutic sequence is still not known, especially for borderline resectable PDAC, and the role of adding SBRT to chemotherapy in the neoadjuvant setting needs to be evaluated in randomised controlled trials. The aim of the STEREOPAC trial is to assess the impact and efficacy of adding isotoxic high-dose SBRT (iHD-SBRT) to neoadjuvant mFFX or Gemcitabine/Nab-Paclitaxel (Gem/Nab-P) in patients with borderline resectable PDAC. METHODS: This is a randomised comparative multicentre phase II trial, planning to enrol patients (n = 256) diagnosed with a borderline resectable biopsy-confirmed PDAC. Patients will receive 4 cycles of mFFX (or 6 doses of Gem/Nab-P). After full disease restaging, non-progressive patients will be randomised for receiving either 4 additional mFFX cycles (or 6 doses of Gem/Nab-P) (Arm A), or 2 mFFX cycles (or 3 doses of Gem/Nab-P) + iHD-SBRT (35 to 55 Gy in 5 fractions) + 2 mFFX cycles (or 3 doses of Gem/Nab-P) (Arm B). Then curative surgery will be performed followed by adjuvant chemotherapy according to patient's condition. The co-primary endpoints are R0 resection and disease-free survival after the complete sequence strategy. The secondary endpoints include resection rate, overall survival, locoregional failure / distant metastasis free interval, pathologic complete response, toxicity, postoperative complications and quality of life assessment. DISCUSSION: This trial will help define the best neoadjuvant treatment sequence for borderline resectable PDAC and aims to evaluate if a total neoadjuvant treatment integrating iHD-SBRT improves the patients' oncological outcomes. TRIAL REGISTRATION: The study was registered at ClinicalTrails.gov (NCT05083247) on October 19th, 2021, and in the Clinical Trials Information System (CTIS) EU CT database (2022-501181-22-01) on July 2022.

Spleen-preserving pancreatectomy with removal of splenic vessels: impact on splenic parenchyma ?

BACKGROUND: While outcomes after spleen-preserving distal pancreatectomy (SP-DP) have been widely reported, impacts on splenic parenchyma have not been well studied. This study aimed to compare postoperative outcomes, particularly spleen-related outcomes, by assessing splenic imaging after SP-DP with or without splenic vessels removal. METHODS: Data for all patients who underwent SP-DP with splenic vessels removal (Warshaw technique, WDP) or preservation (Kimura technique, KDP) between 2010 and 2022 in two tertiary centres were retrospectively analysed. Splenic ischemia and volume at early/late imaging and postoperative outcomes were reviewed. RESULTS: Eighty-seven patients were included, 51 in the WDP and 36 in the KDP groups. Median Charlson's Comorbidity Index was significantly higher in the WDP group compared with the KDP group. Postoperative morbidity was similar between groups. There was more splenic ischemia at early imaging in the WDP group compared to the KDP group (55% vs. 14%, p = 0.018), especially severe ischemia (23% vs. 0%). Partial splenic atrophy was observed in 29% and 0% in the WDP and KDP groups, respectively (p = 0.002); no complete splenic atrophy was observed. Platelet levels at POD 1, 2 and 6 were significantly higher in the WDP group compared to KDP group. At univariate analysis, age, Charlson Comorbidity Index, platelet levels at POD 6, and early splenic infarction were prognostic factors for development of splenic atrophy. No episodes of overwhelming post-splenectomy infection or secondary splenectomy were recorded after a median follow-up of 9 and 11 months in the WDP and KDP groups, respectively. CONCLUSIONS: Splenic ischemia appeared in one-half of patients undergoing SP-DP with splenic vessels removal at early imaging, and partial splenic atrophy in almost 30% at late imaging, without clinical impact or complete splenic atrophy. Age, Charlson Comorbidity Index, platelet levels at POD 6, and early splenic infarction could help to predict the occurrence of splenic atrophy.

SMAD4 Positive Pancreatic Ductal Adenocarcinomas Are Associated with Better Outcomes in Patients Receiving FOLFIRINOX-Based Neoadjuvant Therapy.

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.

Long-Term Outcomes 10 Years after Laparoscopic Sleeve Gastrectomy: a Single Center Retrospective Analysis.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is the most frequently performed bariatric procedure in the world. The aim of the study was to evaluate outcomes after 10 years. METHODS: Patients who underwent LSG between 2005 and 2010 in a single center were retrospectively assessed, focusing mainly on the percentage of excess weight loss (%EWL) after 10 years. Inadequate weight loss was defined as a %EWL < 50% or the need to perform a revisional bariatric surgery. RESULTS: Overall, 149 patients underwent LSG, with a median preoperative body mass index of 42.0 ± 6.5 kg/m2. Ten patients (6.7%) underwent previous bariatric procedure. Patients eating behavior was described as volume eaters in 73 (49%), sweet eaters in 11 (7.4%) and both volume and sweet eaters in 65 (43.6%). Six patients died during follow-up and 25 patients were lost to follow-up, leaving 118 (79%) patients who completed full follow-up. Thirty-five patients (23.5%) needed a revisional bariatric surgery. For the 83 remaining patients, the mean %EWL was 35.9% at 10 years, only 23 of 83 patients (27.7%) had a %EWL ≥ 50%. Thus 80.5% patients (95/118) experienced inadequate weight loss 10 years after LSG. A lower %EWL after 1 year was predictive for inadequate weight loss after 10 years. CONCLUSION: Ten years after LSG, the rate of inadequate weight loss was high, reaching 80% of patients. Thirty percent of patients required a revisional bariatric procedure. New studies must try to identify patients who are good candidates for LSG and strategies to improve long-term outcomes.

Neoadjuvant chemotherapy associated with isotoxic high-dose stereotactic body radiotherapy does not increase postoperative complications after pancreaticoduodenectomy for nonmetastatic pancreatic cancer.

BACKGROUND AND OBJECTIVES: The role of radiotherapy in the therapeutic sequence of nonmetastatic pancreatic cancer (PC) is controversial, including isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT). This study aimed to compare postoperative outcome of patients with nonmetastatic PC undergoing neoadjuvant treatment (NAT) including iHD-SBRT versus upfront pancreaticoduodenectomy (PD). METHODS: All patients undergoing PD for PC from 2017 to 2021 were retrospectively analyzed, identifying patients receiving NAT with iHD-SBRT. Toxicity of treatments and postoperative outcome were assessed and analyzed in a propensity score-matched population. RESULTS: Eighty-nine patients underwent upfront surgery (surgery group) and 22 after NAT and iHD-SBRT (SBRT group). No major side effects SBRT-related were identified preoperatively. Postoperative morbidity was similar between groups. There was no postoperative death in SBRT group, and six in surgery group (p = 0.597). No difference was observed in the rates of complications related to pancreatic surgery. The postoperative hospital stay was shorter in SBRT versus surgery groups (p = 0.016). After propensity score matching, no significant difference in the postoperative morbidity was observed between groups. CONCLUSIONS: Incorporation of iHD-SBRT in the NAT sequence before PD for PC did not increase postoperative morbidity compared with upfront surgery. These results confirm the feasibility and safety of iHD-SBRT for the upcoming STEREOPAC trial.

Combination, Modulation and Interplay of Modern Radiotherapy with the Tumor Microenvironment and Targeted Therapies in Pancreatic Cancer: Which Candidates to Boost Radiotherapy?

Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly diverse disease with low tumor immunogenicity. PDAC is also one of the deadliest solid tumor and will remain a common cause of cancer death in the future. Treatment options are limited, and tumors frequently develop resistance to current treatment modalities. Since PDAC patients do not respond well to immune checkpoint inhibitors (ICIs), novel methods for overcoming resistance are being explored. Compared to other solid tumors, the PDAC's tumor microenvironment (TME) is unique and complex and prevents systemic agents from effectively penetrating and killing tumor cells. Radiotherapy (RT) has the potential to modulate the TME (e.g., by exposing tumor-specific antigens, recruiting, and infiltrating immune cells) and, therefore, enhance the effectiveness of targeted systemic therapies. Interestingly, combining ICI with RT and/or chemotherapy has yielded promising preclinical results which were not successful when translated into clinical trials. In this context, current standards of care need to be challenged and transformed with modern treatment techniques and novel therapeutic combinations. One way to reconcile these findings is to abandon the concept that the TME is a well-compartmented population with spatial, temporal, physical, and chemical elements acting independently. This review will focus on the most interesting advancements of RT and describe the main components of the TME and their known modulation after RT in PDAC. Furthermore, we will provide a summary of current clinical data for combinations of RT/targeted therapy (tRT) and give an overview of the most promising future directions.

Perioperative antimicrobial prophylaxis in patients undergoing pancreatoduodenectomy: retrospective analysis of bacteriological profile and susceptibility.

BACKGROUND: Pancreatic tumours are frequently associated with obstructive jaundice requiring preoperative biliary drainage (PBD) before pancreatoduodenectomy (PD), exposing patients to infectious complications. This study aims to compare postoperative complications after PD with or without PBD and to analyse bile bacteriology and antibiotic susceptibility. METHODS: All patients undergoing PD between 2014 and 2019 were retrospectively evaluated, and postoperative outcomes were compared according to PBD use. Prophylactic narrow-spectrum antibiotic therapy was given for 24 h, then adapted according to bacteriologic profile. Intraoperative bile cultures and antibiograms were collected. RESULTS: Among 164 patients with intraoperative bile culture during PD (75 PBD+, 89 PBD-), an infected bile was observed in 95% and 70% of PBD + and PBD- groups, respectively (p < 0.001). Postoperative mortality and severe morbidity including infectious complications were similar between groups (5% and 15%). The median duration of antibiotherapy was longer in PBD + compared to PBD- groups (9 vs. 2 days, p = 0.009). Malignant indication and PBD were associated with bile contamination using univariate analysis, and PBD was significantly relevant at multivariate analysis. Most common pathogens identified in bile cultures were Escherichia coli, Klebsiella spp. and Enterobacter spp. Overall antibiotic susceptibility to commonly used antibiotics was decreased, including those used in our local guidelines. CONCLUSIONS: PBD exposes nearly 100% of patients undergoing PD to bile infection and an increased duration of postoperative antimicrobial therapy, without increasing infectious complications in this study. Adaptation of antimicrobial prophylaxis should be further evaluated according to performance of PBD and local epidemiology, in order to avoid overuse of antibiotics.

Peritoneal patch in vascular reconstruction during pancreaticoduodenectomy for pancreatic cancer: a single Centre experience.

BACKGROUND: Concomitant venous resection during pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma with mesenterico-portal vein involvement is increasingly performed to achieve oncological resection. This study aims to report a single centre experience in peritoneal patch (PP) as autologous graft for vascular reconstruction (VR) during PD. METHODS: A retrospective analysis of all patients who underwent PD + VR with PP between December 2019 and September 2020 was performed, using a prospective collected database. Postoperative outcome and pathological margins were evaluated. Venous patency was assessed by computed tomography at day 7 and week 12 post surgery. RESULTS: Fifteen patients underwent PD + VR with PP reconstruction for pancreatic cancer, including one total pancreatectomy. VR consisted of lateral (n = 14) or tubular (n = 1) patch. The median PP length was 30 mm [26.3-33.8] and venous clamping time 30 min [27.5-39.0]. Computed tomography showed a patent VR in 93.3% and 53.3% after 7 days and 12 weeks, respectively; venous patency loss was always asymptomatic. The only postoperative VR-related complication was one mesenteric venous thrombosis. Five other patients experienced VR-unrelated complications: septic shock (n = 3), biliary fistula (n = 1) and post-traumatic subdural hematoma (n = 1). Mortality was nihil. At pathology, R0 resection (≥1 mm) was observed in 40.0% (6/15), venous margin was free in 46.7% (7/15), and venous wall was involved in 40.0% (6/15). CONCLUSIONS: Use of PP as venous substitute during PD + VR is safe and feasible with an acceptable postoperative morbidity, and a decreased but asymptomatic venous patency after 12 weeks which should question the role of anticoagulation therapy.

A Comprehensive Review of the Potential Role of Liquid Biopsy as a Diagnostic, Prognostic, and Predictive Biomarker in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma is one of the most lethal malignant diseases, with a mortality rate being close to incidence. Due to its heterogeneity and plasticity, as well as the lack of distinct symptoms in the early phases, it is very often diagnosed at an advanced stage, resulting in poor prognosis. Traditional tissue biopsies remain the gold standard for making a diagnosis, but have an obvious disadvantage in their inapplicability for frequent sampling. Blood-based biopsies represent a non-invasive method which potentially offers easy and repeated sampling, leading to the early detection and real-time monitoring of the disease and hopefully an accurate prognosis. Given the urgent need for a reliable biomarker that can estimate a patient's condition and response to an assigned treatment, blood-based biopsies are emerging as a potential new tool for improving patients' survival and surveillance. In this article, we discuss the current advances and challenges in using liquid biopsies for pancreatic cancer, focusing on circulating tumour DNA (ctDNA), extracellular vesicles (EVs), and circulating tumour cells (CTCs), and compare the performance and reliability of different biomarkers and combinations of biomarkers.

Isotoxic High-Dose Stereotactic Body Radiotherapy (iHD-SBRT) Versus Conventional Chemoradiotherapy for Localized Pancreatic Cancer: A Single Cancer Center Evaluation.

Given the lack of direct comparative evidence, we aimed to compare the oncological outcomes of localized pancreatic ductal adenocarcinoma (PDAC) treated in the same tertiary cancer center with isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) or conventional chemoradiotherapy (CRT). Biopsy-proven borderline/locally advanced patients treated with iHD-SBRT (35 Gy in 5 fractions with a simultaneous integrated boost up to 53 Gy) or CRT (45−60 Gy in 25−30 fractions) were retrospectively included from January 2006 to January 2021. The median overall survival (mOS) was evaluated trough uni- and multivariate analyses. The progression free survival (PFS) and the 1-year local control (1-yLC) were also reported. Eighty-two patients were included. The median follow-up was 19.7 months. The mOS was in favour of the iHD-SBRT group (22.5 vs. 15.9 months, p < 0.001), including after multivariate analysis (HR 0.39 [CI95% 0.18−0.83], p = 0.014). The median PFS and the 1-yLC were also significantly better for iHD-SBRT (median PFS: 16.7 vs. 11.5 months, p = 0.011; 1-yLC: 75.8 vs. 39.3%, p = 0.004). In conclusion, iHD-SBRT is a promising RT option and may offer an improvement in OS in comparison to CRT for localized PDAC. Further validation is required to confirm the exact role of iHD-SBRT and the optimal therapeutic sequence for the treatment of localized PDAC.

Opioid-free versus opioid-based anesthesia in pancreatic surgery.

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 < 0.001) and opioid consumption (36 [24-52] vs 10 [2-24], P = 0.005) were both less in the OFA group. Length of stay was shorter by 4 days with OFA (14 [7-46] vs 10 [6-16], P < 0.001). OFA (P = 0.03), with postoperative pancreatic fistula (P = 0.0002) and delayed gastric emptying (P < 0.0001) were identified as only independent factors for length of stay. The comprehensive complication index (CCI) was the lowest with OFA (24.9 ± 25.5 vs 14.1 ± 23.4, P = 0.03). There were no differences in demographics, operative time, blood loss, bradycardia, vasopressors administration or time to extubation among groups. CONCLUSIONS: In this series, OFA during pancreatic resection is feasible and independently associated with a better outcome, in particular pain outcomes. The lower rate of postoperative complications may justify future randomized trials to test the hypothesis that OFA may improve outcomes and shorten length of stay.

Colorectal resection in end-stage renal disease (ESRD) patients: experience from a single tertiary center.

BACKGROUND: End-stage renal disease (ESRD) and renal replacement therapy (RRT) are important risk factors for post-operative morbidity and mortality but remains poorly reported in colorectal surgery. This study aims to evaluate postoperative outcomes of ESRD patients under RRT undergoing colorectal resection. METHODS: All ESRD patients under RRT who underwent colorectal resection between 2006 and 2019 were retrospectively reviewed. Perioperative outcomes were analysed, such as risk factors of postoperative complications. RESULTS: Forty-two patients were analysed, including 27 emergency and 15 elective surgeries. The most frequent indication was acute colonic ischemia for emergency and malignancy for elective procedures. Laparoscopic approach was used in 12 patients (29%), without difference between elective and emergency groups. Postoperative severe complications rate (including deaths) was 50% (21/42), including 56% (15/27) and 40% (6/15) in emergency and elective groups, respectively (p = .334). Anastomotic leak was observed in 3 of the 23 patients (13%) undergoing digestive anastomosis, (1 in emergency and 2 in elective groups, p = .246). The postoperative mortality rate was 29%, not significantly different between groups. The median hospital stay was 14.5 days (8-42). At univariate analysis, history of cardiac event (p = .028) and open approach (p = .040) were associated with severe complications, and ASA score >3 (p = .043), history of cardiac event (p = .001) and diabetes (p = .030) associated with mortality. CONCLUSIONS: Colorectal surgery in ESRD patient exposes to high risk of morbidity and mortality, even in the elective setting, especially in patients with comorbidities like cardiac event and diabetes. Careful patient selection and closed management is required in such fragile patients.

Pancreatic medullary carcinoma developed on a pancreatic intraductal papillary mucinous neoplasm with loss of MSH2 and MSH6 expression: a case report.

BACKGROUND: Pancreatic medullary carcinoma (PMC) is a rare pancreatic tumor, usually showing the presence of microsatellite instability, mostly MLH1 silencing, and a wild-type KRAS mutation status. We report here a PMC arising from a Pancreatic Intraductal Papillary Mucinous Neoplasm (IPMN), both having KRAS and TP53 mutations. CASE PRESENTATION: We report the case of a 73-year-old woman presenting with right iliac fossa pain. MRI revealed a 16 mm diameter mass in the pancreas, leading to a pancreatic duct stricture and upstream a dilatation of the distal pancreatic duct of Wirsung. A fine needle aspiration was performed, and pathology analysis revealed malignant glandular cells. The patient underwent distal pancreatectomy. Gross examination revealed an12 mm indurated white lesion, adjacent to a cystic lesion extending into the rest of the pancreatic body. Microscopically, the cystic area represented a mixed (gastric-type and pancreatobiliary-type) IPMN, involving the main and secondary pancreatic ducts with low-grade and high-grade dysplasia. In the periphery of this IPMN, a 14mm associated invasive carcinoma was observed, characterized by focal gland formation and by poorly differentiated cells with a syncytial appearance, associated with a dense lymphoplasmocytic and neutrophilic infiltrate. Immunohistochemical analyses showed loss of MSH2 and MSH6 expression. Microsatellite instability was confirmed by molecular test. Molecular analysis was performed both on the invasive carcinoma and on the high-grade dysplasia IPMN, revealing the same mutation profile with KRAS and TP53 mutations. The proposed diagnosis was mixed IPMN with associated invasive medullary carcinoma that presented loss of MSH2 and MSH6 expression. CONCLUSIONS: The present case reports for the first time, at the best of our knowledge, the coexistence of IPMN lesions and PMC, both having the same molecular alterations. It also describes the second case of PMC with microsatellite instability, MSH2 and MSH6 silenced.

Isotoxic high-dose stereotactic body radiotherapy integrated in a total multimodal neoadjuvant strategy for the treatment of localized pancreatic ductal adenocarcinoma.

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.

Impact of COVID-19 Lockdown on Short-Term Results After Laparoscopic Sleeve Gastrectomy.

BACKGROUND: The recent COVID-19 pandemic has led several countries worldwide to confine the population. Consequently, people's mobility and physical activity are limited in addition to a negative psychosocial effect. The aim of this study was to assess the impact of COVID-19 crisis on short-term weight loss and the remission of obesity-associated comorbidities in patients undergoing sleeve gastrectomy (SG). METHODS: A case-control study was conducted comparing percentage of total weight loss (%TWL), excess weight lost (%EWL), and the remission rate of obesity-related comorbidities at the first postoperative year between patients who underwent primary SG between June 2019 and October 2019 (1-year postoperative period affected by COVID-19 lockdown; COV-group), and a control group operated between June 2018 and October 2018 (1-year postoperative period not affected by COVID-19 lockdown; CONTROL-group). RESULTS: In total, 45 patients from COV-group were compared to 57 patients from CONTROL-group. Demographic data were similar between groups. The follow-up rate at 1 year was 100%. The mean %TWL and %EWL was lower at 28.2 ± 12.7% and 67.6 ± 23.5% in COV-group patients compared to 34.3 ± 14.1% and 78.3 ± 27.2% in CONTROL-group patients at 1 year from SG (p=0.025 and p=0.036, respectively). The remission rate of obesity-related comorbidities at 1 year from SG including type 2 diabetes mellitus, hypertension, dyslipidemia, and obstructive sleep apnea syndrome was 57.1%, 60.0%, 71.4%, and 41.7% in COV-group and 66.7%, 72.4%, 85.3%, and 52.9% in CONTROL-group, respectively, without any statistically significant difference between groups. CONCLUSIONS: The COVID-19 lockdown had a negative effect on weight loss in the first year after SG. Larger studies are needed to confirm these results, and we are expecting for a longer follow-up to evaluate the long-term impact on weight loss and comorbidities.

Laparoscopic Management of Blunt and Penetrating Abdominal Trauma: A Single-Center Experience and Review of the Literature.

Introduction: Trauma is a leading cause of death in young patients. The prevalence of blunt and penetrating trauma varies widely across the globe. Similarly, the global experience with laparoscopy in trauma patients also varies. There is a growing body of evidence to suggest that laparoscopy is feasible in trauma patients. We sought to contribute to these data by reporting our experience with laparoscopic management of blunt and penetrating trauma in a Belgian center. Materials and Methods: We retrospectively collected data on all trauma patients admitted to the Saint-Pierre University Hospital in Brussels, Belgium, over the 4-year period from January 2014 to December 2017. Hospital records for patients subjected to exploratory laparoscopy were retrospectively reviewed, and a descriptive analysis was reported. Results: There were 26 patients at a mean age of 40 years treated with laparoscopic exploration for injuries from blunt trauma (7), stab wounds (14), and gunshot injuries (5). The median interval between the arrival at the emergency unit and diagnostic laparoscopy was 175 minutes (range: 27-1440), and the median duration of operation was 119 minutes (range: 8-300). In all patients who underwent laparoscopy for trauma, there were 27% overall morbidity, no mortality, 11% reoperation rate, 7.4% conversions, and 19% incidence of negative laparoscopy. The median intensive care unit stay was 3 days (range: 0-41), and median total hospital stay was 7 days (range: 2-78). Conclusions: Laparoscopy is a safe, feasible, and effective tool in the surgical armamentarium to treat hemodynamically stable patients with blunt and penetrating abdominal trauma. It allows complete and thorough evaluation of intra-abdominal viscera, reduces the incidence of nontherapeutic operations, and allows therapeutic intervention to repair a variety of injuries. However, it requires appropriate surgeon training and experience with advanced laparoscopic techniques to ensure good outcomes.