Recurrence After Surgery for Primary Hyperparathyroidism in 517 Patients With Multiple Endocrine Neoplasia Type 1: An Association Francophone de Chirurgie Endocrinienne and Groupe d'étude des Tumeurs Endocrines study.

OBJECTIVE: To assess recurrence according to the type of surgery for primary hyperparathyroidism (pHPT) in multiple endocrine neoplasia type 1 ( MEN1 ) patients and to identify the risk factors for recurrence after the initial surgery. BACKGROUND: In MEN1 patients, pHPT is multiglandular, and the optimal extent of initial parathyroid resection influences the risk of recurrence. METHODS: MEN1 patients who underwent initial surgery for pHPT between 1990 and 2019 were included. Persistence and recurrence rates after less than subtotal parathyroidectomy (LTSP) and subtotal parathyroidectomy (STP) were analyzed. Patients with total parathyroidectomy with reimplantation were excluded. RESULTS: Five hundred seventeen patients underwent their first surgery for pHPT: 178 had LTSP (34.4%) and 339 STP (65.6%). The recurrence rate was significantly higher after LTSP (68.5%) than STP (45%) ( P < 0.001). The median time to recurrence after pHPT surgery was significantly shorter after LTSP than after STP: 4.25 (1.2-7.1) versus 7.2 (3.9-10.1) years ( P < 0.001). A mutation in exon 10 was an independent risk factor of recurrence after STP (odds ratio = 2.19; 95% CI: 1.31; 3.69; P = 0.003). The 5 and 10-year recurrent pHPT probabilities were significantly higher in patients after LTSP with a mutation in exon 10 (37% and 79% vs 30% and 61%; P = 0.016). CONCLUSIONS: Persistence, recurrence of pHPT, and reoperation rate are significantly lower after STP than LTSP in MEN1 patients. Genotype seems to be associated with the recurrence of pHPT. A mutation in exon 10 is an independent risk factor for recurrence after STP, and LTSP may not be recommended when exon 10 is mutated.

Robotic surgery for inguinal and ventral hernia repair: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis assessed the effectiveness of robotic surgery compared to laparoscopy or open surgery for inguinal (IHR) and ventral (VHR) hernia repair. METHODS: PubMed and EMBASE were searched up to July 2022. Meta-analyses were performed for postoperative complications, surgical site infections (SSI), seroma/hematoma, hernia recurrence, operating time (OT), intraoperative blood loss, intraoperative bowel injury, conversion to open surgery, length of stay (LOS), mortality, reoperation rate, readmission rate, use of opioids, time to return to work and time to return to normal activities. RESULTS: Overall, 64 studies were selected and 58 were used for pooled data analyses: 35 studies (227 242 patients) deal with IHR and 32 (158 384 patients) with VHR. Robotic IHR was associated with lower hernia recurrence (OR 0.54; 95%CI 0.29, 0.99; I2: 0%) compared to laparoscopic IHR, and lower use of opioids compared to open IHR (OR 0.46; 95%CI 0.25, 0.84; I2: 55.8%). Robotic VHR was associated with lower bowel injuries (OR 0.59; 95%CI 0.42, 0.85; I2: 0%) and less conversions to open surgery (OR 0.51; 95%CI 0.43, 0.60; I2: 0%) compared to laparoscopy. Compared to open surgery, robotic VHR was associated with lower postoperative complications (OR 0.61; 95%CI 0.39, 0.96; I2: 68%), less SSI (OR 0.47; 95%CI 0.31, 0.72; I2: 0%), less intraoperative blood loss (- 95 mL), shorter LOS (- 3.4 day), and less hospital readmissions (OR 0.66; 95%CI 0.44, 0.99; I2: 24.7%). However, both robotic IHR and VHR were associated with significantly longer OT compared to laparoscopy and open surgery. CONCLUSION: These results support robotic surgery as a safe, effective, and viable alternative for IHR and VHR as it can brings several intraoperative and postoperative advantages over laparoscopy and open surgery.

Surgery for Primary Aldosteronism in France From 2010 to 2020 - Results from the French-Speaking Association of Endocrine Surgery (AFCE): Eurocrine Study Group.

OBJECTIVE: Describe the diagnostic workup and postoperative results for patients treated by adrenalectomy for primary aldosteronism in France from 2010 to 2020. BACKGROUND: Primary aldosteronism (PA) is the underlying cause of hypertension in 6% to 18% of patients. French and international guidelines recommend CT-scan and adrenal vein sampling as part of diagnostic workup to distinguish unilateral PA amenable to surgical treatment from bilateral PA that will require lifelong antialdosterone treatment.Adrenalectomy for unilateral primary aldosteronism has been associated with complete resolution of hypertension (no antihypertensive drugs and normal ambulatory blood pressure) in about one-third of patients and complete biological success in 94% of patients.These results are mainly based on retrospective studies with short follow-up and aggregated patients from various international high-volume centers. METHODS: Here we report results from the French-Speaking Association of Endocrine Surgery (AFCE) using the Eurocrine® Database. RESULTS: Over 11 years, 385 patients from 10 medical centers were eligible for analysis, accounting for >40% of adrenalectomies performed in France for primary aldosteronism over the period.Preoperative workup was consistent with guidelines for 40% of patients. Complete clinical success (CCS) at the last follow-up was achieved in 32% of patients, and complete biological success was not sufficiently assessed.For patients with 2 follow-up visits, clinical results were not persistent at 1 year for one-fifth of patients.Factors associated with CCS on multivariate analysis were body mass index, duration of hypertension, and number of antihypertensive drugs. CONCLUSIONS: These results call for an improvement in thorough preoperative workup and long-term follow-up of patients (clinical and biological) to early manage hypertension and/or PA relapse.

Pancreatoduodenectomy Following Preoperative Biliary Drainage Using Endoscopic Ultrasound-Guided Choledochoduodenostomy Versus a Transpapillary Stent: A Multicenter Comparative Cohort Study of the ACHBT-FRENCH-SFED Intergroup.

BACKGROUND: It is unclear whether preoperative biliary drainage (PBD) by endoscopic retrograde cholangiopancreatography (ERCP) is equivalent to electrocautery-enhanced lumen-apposing metal stent (ECE-LAMS) before pancreatoduodenectomy (PD). METHODS: Patients who underwent PBD for distal malignant biliary obstruction (DMBO) followed by PD were retrospectively included in nine expert centers between 2015 and 2022. ERCP or endoscopic ultrasound-guided choledochoduodenostomy with ECE-LAMS were performed. In intent-to-treat analysis, patients drained with ECE-LAMS were considered the study group (first-LAMS group) and those drained with conventional transpapillary stent the control group (first-cannulation group). The rates of technical success, clinical success, drainage-related complications, surgical complications, and oncological outcomes were analyzed. RESULTS: Among 156 patients, 128 underwent ERCP and 28 ECE-LAMS in first intent. The technical and clinical success rates were 83.5% and 70.2% in the first-cannulation group versus 100% and 89.3% in the first-LAMS group (p = 0.02 and p = 0.05, respectively). The overall complication rate over the entire patient journey was 93.7% in first-cannulation group versus 92.0% in first-LAMS group (p = 0.04). The overall endoscopic complication rate was 30.5% in first-cannulation group versus 17.9% in first-LAMS group (p = 0.25). The overall complication rate after PD was higher in the first-cannulation group than in the first-LAMS group (92.2% versus 75.0%, p = 0.016). Overall survival and progression-free survival did not differ between the groups. CONCLUSIONS: PBD with ECE-LAMS is easier to deploy and more efficient than ERCP in patients with DMBO. It is associated with less surgical complications after pancreatoduodenectomy without compromising the oncological outcome.

Periostin- and podoplanin-positive cancer-associated fibroblast subtypes cooperate to shape the inflamed tumor microenvironment in aggressive pancreatic adenocarcinoma.

Cancer-associated fibroblasts (CAFs) are orchestrators of the pancreatic ductal adenocarcinoma (PDAC) microenvironment. Previously we described four CAF subtypes with specific molecular and functional features. Here, we have refined our CAF subtype signatures using RNAseq and immunostaining with the goal of defining bioinformatically the phenotypic stromal and tumor epithelial states associated with CAF diversity. We used primary CAF cultures grown from patient PDAC tumors, human data sets (in-house and public, including single-cell analyses), genetically engineered mouse PDAC tissues, and patient-derived xenografts (PDX) grown in mice. We found that CAF subtype RNAseq signatures correlated with immunostaining. Tumors rich in periostin-positive CAFs were significantly associated with shorter overall survival of patients. Periostin-positive CAFs were characterized by high proliferation and protein synthesis rates and low α-smooth muscle actin expression and were found in peri-/pre-tumoral areas. They were associated with highly cellular tumors and with macrophage infiltrates. Podoplanin-positive CAFs were associated with immune-related signatures and recruitment of dendritic cells. Importantly, we showed that the combination of periostin-positive CAFs and podoplanin-positive CAFs was associated with specific tumor microenvironment features in terms of stromal abundance and immune cell infiltrates. Podoplanin-positive CAFs identified an inflammatory CAF (iCAF)-like subset, whereas periostin-positive CAFs were not correlated with the published myofibroblastic CAF (myCAF)/iCAF classification. Taken together, these results suggest that a periostin-positive CAF is an early, activated CAF, associated with aggressive tumors, whereas a podoplanin-positive CAF is associated with an immune-related phenotype. These two subpopulations cooperate to define specific tumor microenvironment and patient prognosis and are of putative interest for future therapeutic stratification of patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Impact of a procalcitonin-based algorithm on the quality of management of patients with uncomplicated adhesion-related small bowel obstruction assessed by a textbook outcome: a multicenter cluster-randomized open-label controlled trial.

BACKGROUND: Acute adhesion-related small bowel obstruction (ASBO) is a common digestive emergency, accounting for 1 to 3% of all digestive emergencies. The efficacy of conservative management in this setting is a subject of debate, as it may delay the decision to perform surgery and increase the frequency of bowel resection (e.g., in the presence of bowel necrosis) or, in contrast, prompt an excessive number of unnecessary laparotomies. Thus, the decision to perform surgery is difficult. We propose that the introduction of the procalcitonin (PCT)-based algorithm improves the quality of the management of patients with ASBO by aiding the decision of whether or not to perform surgery. METHODS: This is a 1:1 cluster-randomized clinical trial (use of algorithm: no algorithm) using an independent computer to ensure that investigators cannot interfere with the randomization. Each cluster will correspond to one investigating center. All patients in a center will be managed in the same way. Before randomization, each principal investigator will provide a commitment to participate in the study to avoid the risk of "empty clusters". The patients included will constitute two parallel arms (use of algorithm versus no algorithm), with no expected crossover between arms. The inclusion criteria are being an adult with uncomplicated acute ASBO (i.e., absence of fever, abdominal pain and distension, nausea and/or vomiting, and the absence of gas and/or stool, in conjunction with a contrast-enhanced CT scan, for patients with previous abdominal surgery) who is able to express consent with a signed written informed consent form. Patients with complicated acute ASBO (strangulation or peritonitis) will be excluded. DISCUSSION: There is an ongoing debate on the management of uncomplicated ASBO. The main points are to avoid a surgery if it is unnecessary and to avoid delayed surgery if it is necessary. Currently, there are no robust criteria to objectively determine the failure of non-surgical treatment or to establish the indications for surgery in acute ASBO. Our team proposes the use of procalcitonin (PCT) to help distinguish patients for whom conservative management is likely to be successful from those for whom surgical management is required. The results from a randomized control trial could help in the selection of patients through clear inclusion and exclusion criteria and simplify or clarify the management algorithm. In conclusion, PCT may be useful in evaluating the proper strategy for ASBO. Trial registration The trial is registered at clinical trials under the reference: NCT03905239.

From abdominal pain to a diagnosis of primary sclerosing encapsulating peritonitis and its management, a case report.

BACKGROUND: Sclerosing Encapsulating peritonitis (SEP) is a rare chronic fibro-inflammatory disease of the peritoneum. The aetiology can be either primary or secondary. The knowledge around this topic is poor. CASE PRESENTATION: Based on the report of a 64-year-old man suffering from intestinal obstruction and its management with a final diagnosis of primary SEP, herein we review the literature concerning this specific entity of primary SEP and its challenge in both diagnosis and treatment. CONCLUSION: whereas SEP is a rare entity, imagery is helpful to make the diagnosis.

Overexpression of sortilin is associated with 5-FU resistance and poor prognosis in colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide. Even if 5-fluorouracil (5-FU) is used as the first-line chemotherapeutic drug, responsiveness is only 20-30%. Acquired resistance to 5-FU contributes to both poor patient prognosis and relapse, emphasizing the need to identify biomarkers. Sortilin, a vacuolar protein sorting 10 protein (Vps10p), implicated in protein trafficking, is over expressed in CRC cell lines cultured 72 hours in presence of 5-FU. This overexpression was also observed in 5-FU-resistant cells derived from these cell lines as well as in CRC primary cultures (or patients derived cell lines). A significantly higher expression of sortilin was observed in vivo, in 5-FU-treated tumours engrafted in Nude mice, as compared with non-treated tumour. A study of transcriptional regulation allowed identifying a decrease in ATF3 expression, as an explanation of sortilin overexpression following 5-FU treatment. In silico analysis revealed SORT1 expression correlation with poor prognosis. Moreover, sortilin expression was found to be positively correlated with CRC tumour grades. Collectively, our findings identify sortilin as a potential biomarker of 5-FU resistance associated with poor clinical outcomes and aggressiveness in CRC. As a new prognostic factor, sortilin expression could be used to fight against CRC.

Impact of Permanent Post-thyroidectomy Hypoparathyroidism on Self-evaluation of Quality of Life and Voice: Results From the National QoL-Hypopara Study.

OBJECTIVE: The aim of this study was to compare the quality of life (mental health) and voice in patients with or without permanent hypoparathyroidism after total thyroidectomy. SUMMARY BACKGROUND DATA: Permanent hypoparathyroidism is an underestimated complication of thyroid surgery owing to suppression of parathormone secretion. Few studies have evaluated the consequences of hypoparathyroidism on quality of life and none has studied its effects on voice. METHODS: The QoL-hypopara study (ClinicalTrial.gov NCT04053647) was a national observational study. Adult thyroidectomized patients were included between January and June 2020. A serum parathormone level <15 pg/mL >6 months after surgery defined permanent hypoparathyroidism. Patients answered the MOS-36-item short-form health (SF-36), the Voice Handicap Index (VHI) surveys, and a list of questions regarding their symptoms. RESULTS: A total of 141 patients were included, 45 with permanent hypoparathyroidism. The median period between thyroid surgery and the questionnaire was 6 (Q1-Q3 4-11) and 4 (4-5) years in hypoparathyroid patients and controls respectively. Hypoparathyroid patients presented a reduced median mental score ratio (SF-36) [0.88 (Q1-Q3 0.63-1.01) vs 1.04 (0.82-1.13), P = 0.003] and a lower voice quality (incidence rate ratio for total VHI 1.83-fold higher, P < 0.001). In multivariable analysis, hypoparathyroidism [-0.17 (95% confidence interval -0.28 to -0.07), P = 0.002], but not age, female sex, thyroid cancer, or abnormal TSH level, was associated with the reduced mental score ratio. Myalgia, joint pain, paresthesia, tetany, anxiety attack, and exhaustion were the most common symptoms among hypoparathyroid patients (>50%). CONCLUSIONS: Hypoparathyroid patients present significantly impaired quality of life, lower voice quality, and frequent symptoms. These results reinforce the importance of preventing this complication.

Partial Versus Total Thyroidectomy: What Influences Most Surgeons' Decision? Analysis of a Nationwide Cohort of 375,810 Patients Over 10 Years.

National and international guidelines about thyroid surgery seem to be moving more and more towards less radical surgical procedures but everyday practice does not seem to always align with them. We describe for the first time the role of non-surgical parameters in the surgeon's choice for thyroid surgery. OBJECTIVE: The ain of this study was to describe thyroid surgery and to identify the factors leading to either a total or a partial thyroidectomy regardless of the severity of the thyroid disease. SUMMARY BACKGROUND DATA: National and international guidelines about thyroid surgery seem to be moving more and more toward less radical surgical procedures but everyday practice does not seem to always align with them. METHODS: We based this nationwide retrospective cohort study on a national database that compiles discharge abstracts for every admission for thyroidectomy to French acute healthcare facilities (PMSI database 2010 to 2019). RESULTS: In this study, 375,810 patients (male: 23%; age = 53 ±â€Š15 years) had a thyroidectomy (partial: 28%) for cancer (17%), hyperthyroidism (16%), nonfunctioning goiter (64%), or other (3%). We noticed a global trend toward more partial thyroidectomy (P < 0.001) with a significant increase in the proportion of lobectomy in the post-ATA recommendations' period (P < 0.001) as well as in the "French Levothyrox crisis" period, in which we saw an unexpected rise of adverse events notifications associated with the marketing of a new formula of Levothyrox (P < 0.001) amid widespread media coverage. In a multivariate analysis, we also identified that complete resection was more frequently performed in centers with a caseload >40/year [P < 0.001, odds ratio (OR) = 1.48], for obese patients (body mass index >30 kg/m2; P < 0.001, OR = 1.42), and according to the indication of surgery (OR benign = 1, OR cancer = 2.25, OR hyperthyroidism = 4.13). CONCLUSION: We describe for the first time the role of non-surgical parameters in the surgeon's choice for thyroid surgery.

Limited Resection Versus Pancreaticoduodenectomy for Duodenal Gastrointestinal Stromal Tumors? Enucleation Interferes in the Debate: A European Multicenter Retrospective Cohort Study.

BACKGROUND: The optimal surgical procedure for duodenal gastrointestinal stromal tumors (D-GISTs) remains poorly defined. Pancreaticoduodenectomy (PD) allows for a wide resection but is associated with a high morbidity rate. OBJECTIVES: The aim of this study was to compare the short- and long-term outcomes of PD versus limited resection (LR) for D-GISTs and to evaluate the role of tumor enucleation (EN). METHODS: In this retrospective European multicenter cohort study, 100 patients who underwent resection for D-GIST between 2001 and 2013 were compared between PD (n = 19) and LR (n = 81). LR included segmental duodenectomy (n = 47), wedge resection (n = 21), or EN (n = 13). The primary objective was to evaluate disease-free survival (DFS) between the groups, while the secondary objectives were to analyze the overall morbidity and mortality, radicality of resection, and 5-year overall survival (OS) and recurrence rates between groups. Furthermore, the short- and long-term outcomes of EN were evaluated. RESULTS: Baseline characteristics were comparable between the PD and LR groups, except for a more frequent D2 tumor location in the PD group (68.3% vs. 29.6%; p = 0.016). Postoperative morbidity was higher after PD (68.4% vs. 23.5%; p < 0.001). OS (p = 0.70) and DFS (p = 0.64) were comparable after adjustment for D2 location and adjuvant therapy rate. EN was performed more in American Society of Anesthesiologists (ASA) stage III/IV patients with tumors < 5 cm and was associated with a 5-year OS rate of 84.6%, without any disease recurrences. CONCLUSIONS: For D-GISTs, LR should be the procedure of choice due to lower morbidity and similar oncological outcomes compared with PD. In selected patients, EN appears to be associated with equivalent short- and long-term outcomes. Based on these results, a surgical treatment algorithm is proposed.

Associations between the severity of medical and surgical complications and perception of surgeon empathy in esophageal and gastric cancer patients.

OBJECTIVE: To assess the impact of global physician empathy and its three subdimensions (establishing rapport, emotional and cognitive processes) on the severity of postoperative complications in a sample of cancer patients. METHODS: We retrospectively analyzed data on 256 patients with esogastric cancer from the French national FREGAT database. Empathy and its subdimensions were assessed using the patient-reported CARE scale and the severity of medical and surgical complications was reported with the Clavien-Dindo classification system. The usual covariates were included in multinomial logistic regression analyses. RESULTS: Physician empathy predicted the odds of reporting major complications. When patients perceived high empathy, they were less likely to report major complications compared to no complications (OR = .95, 95% CI = [.91-.99], p = .029). Among the three dimensions, only "establishing rapport" (OR = .84, 95% CI = [.73-.98], p = .019) and the "emotional process" (OR = .85, 95% CI = [.74-.98], p = .022) predicted major complications. CONCLUSIONS: Physician empathy is essential before surgery. Further research is needed to understand the mechanisms associating empathy with health outcomes in cancer. Physicians should be trained to establish good rapport with patients, especially in the preoperative period.

Implantation of biologic mesh in ventral hernia repair-does it make sense?

BACKGROUND: Biological acellular porcine dermis mesh, such as Permacol™, has been used since 2009 to treat abdominal incisional hernias in a septic context. This study investigated the risk factors for incisional hernia recurrence after biological mesh augmentation. RESULTS: Over a period of 6 years from February 2009 to February 2015, 68 patients underwent surgery. The mesh was placed intraperitoneally with closure of the anterior fascia in 27 cases (39.7%). The biological mesh was placed in the retromuscular pre-fascial plane in 1 case (1.5%) and pre-aponeurotic plane in 1 case (1.5%). Closure of the anterior fascia was not achieved in 39 cases, including 20 cases in which the mesh was placed intraperitoneally (intraperitoneal bridging group, 29.4%) and 19 cases in which the mesh was placed between the edges of the fascia (inlay bridging group, 27.9%). There were 37 cases of postoperative surgical site infections (54.4%), and Clavien-Dindo morbidity staging indicated stage I-II and III-IV complications in 19.1% and 44.1% of the cases, respectively. The recurrence rate was 61.8%, and the mortality rate was 0%. The rate of recurrence was significantly lower in the «fascia approximated¼ group (37%), p = 0.001). Univariate analyses of risk factors for procedural failure indicated an increased risk of recurrence in cases of postoperative surgical site infections, complications of Clavien-Dindo grade III or higher, an absent fascial closure in front of the mesh (OR = 8.69), an operating time longer than 180 min, and a VHWG score higher than 2. After logistic regression, the risk factors for recurrence were postoperative infections (OR = 6.2), placement of bridged biological mesh (OR = 22.3), and postoperative morbidity grade III or higher (OR = 16.7). CONCLUSIONS: Patients with postoperative surgical site infections are at an increased risk for recurrence, and bridged mesh placements lack efficacy. Overall, this study challenges the purported advantage of biologics in treating incisional hernia repairs.

Pancreatoduodenectomy for Neuroendocrine Tumors in Patients with Multiple Endocrine Neoplasia Type 1: An AFCE (Association Francophone de Chirurgie Endocrinienne) and GTE (Groupe d'étude des Tumeurs Endocrines) Study.

AIM: To assess postoperative complications and control of hormone secretions following pancreatoduodenectomy (PD) performed on multiple endocrine neoplasia type 1 (MEN1) patients with duodenopancreatic neuroendocrine tumors (DP-NETs). BACKGROUND: The use of PD to treat MEN1 remains controversial, and evaluating the right place of PD in MEN1 disease makes sense. METHODS: Thirty-one MEN1 patients from the Groupe d'étude des Tumeurs Endocrines MEN1 cohort who underwent PD for DP-NETs between 1971 and 2013 were included. Early and late postoperative complications, secretory control and overall survival were analyzed. RESULTS: Indication for surgery was: Zollinger-Ellison syndrome (n = 18; 58%), nonfunctioning tumor (n = 9; 29%), insulinoma (n = 2; 7%), VIPoma (n = 1; 3%) and glucagonoma (n = 1; 3%). Mean follow-up was 141 months (range 0-433). Pancreatic fistulas occurred in 5 patients (16.1%), distant metastases in 6 (mean onset of 43 months; range 13-110 months), postoperative diabetes mellitus in 7 (22%), and pancreatic exocrine insufficiency in 6 (19%). Five-year overall survival was 93.3% [CI 75.8-98.3] and ten-year overall survival was 89.1% [CI 69.6-96.4]. After a mean follow-up of 151 months (range 0-433), the biochemical cure rate for MEN-1 related gastrinomas was 61%. CONCLUSION: In MEN1 patients, pancreatoduodenectomy can be used to control hormone secretions (gastrin, glucagon, VIP) and to remove large NETs. PD was found to control gastrin secretions in about 60% of cases.

5-Fluorouracil resistance mechanisms in colorectal cancer: From classical pathways to promising processes.

Colorectal cancer (CRC) is a public health problem. It is the third most common cancer in the world, with nearly 1.8 million new cases diagnosed in 2018. The only curative treatment is surgery, especially for early tumor stages. When there is locoregional or distant invasion, chemotherapy can be introduced, in particular 5-fluorouracil (5-FU). However, the disease can become tolerant to these pharmaceutical treatments: resistance emerges, leading to early tumor recurrence. Different mechanisms can explain this 5-FU resistance. Some are disease-specific, whereas others, such as drug efflux, are evolutionarily conserved. These mechanisms are numerous and complex and can occur simultaneously in cells exposed to 5-FU. In this review, we construct a global outline of different mechanisms from disruption of 5-FU-metabolic enzymes and classic cellular processes (apoptosis, autophagy, glucose metabolism, oxidative stress, respiration, and cell cycle perturbation) to drug transporters and epithelial-mesenchymal transition induction. Particular interest is directed to tumor microenvironment function as well as epigenetic alterations and miRNA dysregulation, which are the more promising processes that will be the subject of much research in the future.

Risk Factors of Redo Surgery After Unilateral Focused Parathyroidectomy: Conclusions From a Comprehensive Nationwide Database of 13,247 Interventions Over 6 Years.

BACKGROUND: Surgical removal of hyperfunctional parathyroid gland is the definitive treatment for primary hyperparathyroidism (pHPT). Postoperative follow-up shows variability in persistent/recurrent disease rate throughout different centers. OBJECTIVE: To evaluate the incidence of redo surgery after targeted parathyroidectomy for pHPT. METHODS: We performed a nationwide retrospective cohort study on the "Programme de Medicalisation des Systemes d'Information," the French administrative database that collects information on all healthcare facilities' discharges. We extracted data from 2009 to 2018 for all patients who underwent parathyroidectomy for pHPT between January 2011 to December 2016. The primary outcome was the reoperation rate within 2 years since first surgery. Patients who had a first attempt of surgery within the previous 24 months, familial hyperparathyroidism, multiglandular disease, and renal failure were excluded. Results were adjusted according to sex and the Elixhauser Comorbidity Index. Operative volume thresholds to define high-volume centers were achieved by the Chi-Squared Automatic Interaction Detector method. RESULTS: In the study period, 13,247 patients (median age 63, F/M=3.6) had a focused parathyroidectomy by open (88.7%) or endoscopic approach. Need of remedial surgery was 2.8% at 2 years. In multivariate analysis, factors predicting redo surgery were: cardiac history (P=0.008), obesity (P=0.048), endoscopic approach (P=0.005), and low-volume center (P<0.001). We evaluated that an annual caseload of 31 parathyroidectomies was the best threshold to discriminate high-volume centers and carries the lowest morbidity/failure rate. CONCLUSION: Although focused parathyroidectomy represents a standardized operation, cure rate is strongly associated with annual hospital caseload, type of procedure (endoscopic), and patients' features (obesity, cardiac history). Patients with risk factors for redo surgery should be considered for an open surgery in a high-volume center.

Extravasation of Noncytotoxic Drugs.

Objective: Commonly used drugs may be dangerous in case of extravasation. The lack of information from health care teams can lead to delays in both diagnosis and treatments. This review aims at alerting health care professionals about drugs and risk factors for extravasation and outlines recommendations for the diagnosis and treatment of extravasation. Data Source: A literature search of MEDLINE/PubMed, Scopus, the Cochrane Library, and Google Scholar was performed from 2000 to December 2019 using the following terms: extravasation, central venous line, peripheral venous line, irritant, and vesicant. Study Selection and Data Extraction: Overall, 140 articles dealing with drug extravasation were considered potentially relevant. Each article was critically appraised independently by 2 authors, leading to the inclusion of 80 relevant studies, guidelines, and reviews. Articles discussing incidents of extravasation in the neonatal and pediatric population of patients were excluded. Data Synthesis: Training of health care teams and writing care protocols are important for an optimal management of extravasations. A prompt consultation should be achieved by a specialist surgeon. The surgical procedure, if necessary, will consist of wound debridement followed by an abundant lavage. Relevance to Patient Care and Clinical Practice: This review discusses the management of drug extravasations according to their mechanism(s) of toxicity on tissues. It highlights the importance of a close monitoring of patients and the training of health care teams likely to face this type of adverse event. Conclusions: Extravasations still contribute to significant morbidity and mortality. A good knowledge of risk factors and the implementation of easily and quickly accessible standardized care protocols are 2 key elements in both prevention and treatment of extravasations.

Results of the FUSE Evaluation Project in France.

BACKGROUND: The Federation of Visceral and Digestive Surgery (FCVD) is in charge in France of the continuing medical education of digestive surgeons. Since 2016 and in collaboration with SAGES, it has offered the Fundamental Use of Surgical Energy (FUSE) program as part of the continuing education for surgeons including eLearning and hands-on workshops. METHODS: The aim of this study was to evaluate the impact of the FUSE program on the participants by participating in a knowledge test and completing a survey. RESULTS: 485 participants fully completed the knowledge test of 18 questions. Post-test assessment showed an increase in the mean score with respect to pre-test assessment, and the surgeons who have participated to the hands-on workshops had a better score. 304 participants filled the survey of 6 questions. The majority were satisfied by the FUSE program and felt that the objectives were achieved. CONCLUSIONS: The FUSE program developed by SAGES and adopted by the FCVD in France was very much appreciated by the participants and achieved its educational objectives. Our goal is to spread it as widely as possible to all members of the operating room team.

What is the ideal indwelling time for metal stents after endoscopic ultrasound-guided gastrojejunostomy? Case report of delayed iatrogenic perforation with a review of the literature.

Several recent studies have described the feasibility, efficacy and safety of the placement of lumen-apposing metal stents (LAMS) for the treatment of gastrointestinal strictures. However, the optimum stent indwelling time is unclear. We reviewed the literature on endoscopic gastroenterostomy (GE) with a focus on the stent indwelling time and we described the first reported case of iatrogenic perforation six months after Axios stent placement. In the literature review (n = 239), the composite technical success rate and clinical success rate were 93.7% and 87.9%, respectively. The mean follow-up period was 191 days, and the mean stent indwelling time was 88 days. Among 13 studies (n = 202), the mean rate of complications was 13.4%. The principal complication was mis-deployment of the stent (4.5%). We report a case report of delayed iatrogenic perforation. A 59-year-old male patient with cystic dystrophy of the duodenum has been followed for several years. He presented with anorexia following duodenal obstruction and underwent endoscopic ultrasound-guided gastrojejunostomy. Six months later, he was referred to our center due to septic shock, and abdominal computed tomography revealed peritonitis secondary to a perforation of the small intestine, opposite the Axios stent. The mean LAMS indwelling time after GE was 88 days. To minimise the rate of adverse events, such as ulceration and mucosal overgrowth, regular abdominal computed tomography and endoscopy can be performed to evaluate the local effect of the stent. When the disease has resolved, the LAMS must be removed as soon as possible.

One-Year Postoperative Mortality in MEN1 Patients Operated on Gastric and Duodenopancreatic Neuroendocrine Tumors: An AFCE and GTE Cohort Study.

IMPORTANCE: In MEN1 patients with gastric and duodenopancreatic neuroendocrine tumors (GPD-NET), surgery aims to control secretions or to prevent metastatic spread, but after GPD-NET resection, postoperative mortality may be related to the surgery itself or to other associated MEN1 lesions with their own uncontrolled secretions or metastatic behavior. OBJECTIVE: To analyze the causes of death within 1 year following a GPD-NET resection in MEN1 patients. DESIGN: An observational study collecting data from the Groupe d'étude des Tumeurs Endocrines (GTE) database. The analysis considered the time between surgery and death (early deaths [<1 month after surgery] versus delayed deaths [beyond 1 month after surgery]) and the period (before 1990 vs after 1990). Causes of death were classified as related to GDP surgery, related to surgery for other MEN1 lesions or not related to MEN1 causes. SETTING: GTE database which includes 1220 MEN1 patients and 441 GPD-NET resections. PARTICIPANTS: Four hundred and forty-one GPD-NET resections. MAIN OUTCOME MEASURES: The primary end point was postoperative mortality within 1 year after surgery. RESULTS: Twenty-four patients met the inclusion criteria (2%). Median age at death was 50.5 years. Sixteen deaths occurred in the 30-day postoperative period (76%). Among the 8 delayed deaths, 3 occurred as a result of medical complications between 30 and 90 postoperative days. After 1990, mean age at death increased from 48 to 58 years (p = 0.09), deaths related to uncontrolled acid secretion disappeared (p < 0.001) and deaths related to associated MEN1 lesions increased from 8 to 54% (p = 0.16). CONCLUSION: Surgery and uncontrolled secretions remain the two main causes of death in MEN1 patients operated for a GPD-NET tumor. Improving the prognosis of these patients requires a strict evaluation of the secretory syndrome and MEN1 aggressiveness before GDP surgery.