Digestive neo-epithelialization after endoscopic stenting for upper digestive tract complete disunion.

BACKGROUND: Complete digestive disunion due to anastomotic necrosis is considered a contraindication to endoscopic repair. However, recent publications have suggested that endoscopic treatment by insertion of a self-expandable metal stent (SEMS) is possible. The report of this patient series aims to demonstrate the use of endoscopic management in selected cases with complete digestive disunion. METHODS: Seven consecutive patients with complete and circumferential upper gastrointestinal anastomotic disunion were treated at two European tertiary care centers between 2009 and 2021 by endoscopic insertion of an SEMS. Treatment was performed with a therapeutic gastroscope under general anesthesia, carbon dioxide insufflation, and fluoroscopic guidance, after surgical or percutaneous drainage. RESULTS: All patients were successfully treated by endoscopic insertion of fully or partially covered SEMS left in place for a median of 8 weeks, with a median of 3 endoscopic sessions. Digestive neo-epithelialization was associated with a restored circumferential gut lumen in all cases. The rate of stent migration was 23% and three patients (43%) experienced symptomatic strictures, which were successfully treated by endoscopic dilation. CONCLUSION: Complete digestive rupture could be successfully treated by endoscopy in selected cases, adding proof-of-concept data regarding guided tissue regeneration alongside SEMS placement.

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.

A Two-Step Diagnostic Approach for NTRK Gene Fusion Detection in Biliary Tract and Pancreatic Adenocarcinomas.

BACKGROUND: It is of interest to determine the incidence and molecular characteristics of NTRK gene fusions in patients with bilio-pancreatic cancers, because of possible treatment with TRK inhibitors for advanced tumors. The aim of the present study was to apply the guidelines for NTRK testing algorithm to a series of patients with bilio-pancreatic cancers. METHODS: Immunohistochemistry screening was applied on formalin-fixed paraffin-embedded archival blocks from surgical resections, biopsies, or cytological samples of biliary tract and pancreatic adenocarcinomas. The presence of at least a weak staining in rare tumor cells led to testing by 2 RNA-based NGS panels. RESULTS: For biliary tract tumors, 153 samples have been selected. A total of 140 samples were suitable to perform IHC, and 17 samples were IHC positive. RNA NGS testing of the 17 IHC-positive samples revealed a single NTRK3 gene fusion (ETV6(4)-NTRK3(14)) that was detected by both NGS panels. In this perihilar cholangiocarcinoma, IHC performed on a biopsy showed a weak focal cytoplasmic and nuclear staining. No other NTRK fusion was detected on the 16 other samples with both panels. Overall in the patients screened by IHC and confirmed by NGS, the percentage of NTRK fusions was 0.7%. For pancreatic cancers, 319 samples have been selected and 297 were suitable to perform IHC. Nineteen samples were IHC positive. No fusion was detected by NGS. CONCLUSION: NTRK gene fusions are rare in bilio-pancreatic cancers but testing is of high interest due to possible treatment with specific TRK inhibitors.

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.

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.

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.

Lean Mass Loss and Altered Muscular Aerobic Capacity after Bariatric Surgery.

INTRODUCTION: Patients undergoing weight loss surgery do not improve their aerobic capacity or peak oxygen uptake (VO2peak) after bariatric surgery and some still complain about asthenia and/or breathlessness. We investigated the hypothesis that a post-surgery muscular limitation could impact the ventilatory response to exercise by evaluating the post-surgery changes in muscle mass, strength, and muscular aerobic capacity, measured by the first ventilatory threshold (VT). METHODS: Thirteen patients with obesity were referred to our university exercise laboratory before and 6 months after bariatric surgery and were matched by sex, age, and height to healthy subjects with normal weight. All subjects underwent a clinical examination, blood sampling, and body composition assessment by dual-energy X-ray absorptiometry, respiratory and limb muscle strength assessments, and cardiopulmonary exercise testing on a cyclo-ergometer. RESULTS: Bariatric surgery resulted in a loss of 34% fat mass, 43% visceral adipose tissue, and 12% lean mass (LM) (p < 0.001). Absolute handgrip, quadriceps, or respiratory muscle strength remained unaffected, while quadriceps/handgrip strength relative to LM increased (p < 0.05). Absolute VO2peak or VO2peak/LM did not improve and the first VT was decreased after surgery (1.4 ± 0.3 vs. 1.1 ± 0.4 L min-1, p < 0.05) and correlated to the exercising LM (LM legs) (R = 0.84, p < 0.001). CONCLUSIONS: Although bariatric surgery has numerous beneficial effects, absolute VO2peak does not improve and the weight loss-induced LM reduction is associated to an altered muscular aerobic capacity, as reflected by an early VT triggering early exercise hyperventilation.

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.

Five-year Outcomes of Sleeve Gastrectomy: A Prospective Multicenter Study.

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.

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.

What Should Guide the Performance of Venous Resection During Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma with Venous Contact?

Complete surgical resection, most often associated with perioperative chemotherapy, is the only way to offer a chance of cure for patients with pancreatic cancer. One of the most important factors in determining survival outcome that can be influenced by the surgeon is the R0 resection. However, the proximity of mesenteric vessels in cephalic pancreatic tumors, especially the mesenterico-portal venous axis, results in an increased risk of vein involvement and/or the presence of malignant cells in the venous bed margin. A concomitant venous resection can be performed to decrease the risk of a positive margin. Given the additional technical difficulty that this implies, many surgeons seek a path between the tumor and the vein, hoping for the absence of tumor infiltration into the perivascular tissue on pathologic analysis, particularly in cases with administration of neoadjuvant therapy. The definition of optimal surgical margin remains a subject of debate, but at least 1 mm is an independent predictor of survival after pancreatic cancer surgical resection. Although preoperative radiologic assessment is essential for accurate planning of a pancreatic resection, intraoperative decision-making with regard to resection of the mesenterico-portal vein in tumors with a venous contact remains unclear and variable. Although venous histologic involvement and perivascular infiltration are not accurately predictable preoperatively, clinicians must examine the existing criteria and normograms to guide their surgical management according to the integration of new imaging techniques, preoperative chemotherapy use, tumor biology and molecular histopathology, and surgical techniques.

Laparoscopic sleeve gastrectomy for morbid obesity in a Belgian-French prospective multicenter study: outcomes and predictors weight loss failure.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) became the most frequently performed bariatric procedure worldwide, gaining rapidly popularity thanks to its technical simplicity and the relatively good results. The aim of this Belgian-French study was to evaluate postoperative complications, weight loss, and resolution of obesity-related comorbidities after LSG, and identify predictive factors of weight loss failure. PATIENTS AND METHODS: A prospective multicenter study was conducted on all LSG performed during 2014 in 7 centers. Their demographic, preoperative, and postoperative data were prospectively collected and analyzed statistically. RESULTS: Overall 529 patients underwent LSG, with a mean preoperative weight and body mass index (BMI) of 118.9 ± 19.9 kg and 42.9 ± 5.5 kg/m2, respectively. Postoperative mortality was null and early postoperative morbidity was 6%, including 2.5% of gastric leakage. BMI significantly decreased to 31.1 kg/m2 and 30.0 kg/m2 at 1 and 3 years, respectively (p < .001). The mean %EWL was 77.2 and 74.6% at 1 and 3 years. A significant reduction in dyslipidemia (28.0-16.8%), obstructive sleep apnea (OSAS) (34.6-23.3%) and arterial hypertension (HTN) (30.4-20.2%) was observed after 3 years, but it does not concern 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: LSG for morbid obesity is safe and effective. Satisfactory outcome after 3 years can be achieved regarding %EWL and some comorbidities such as 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.