Ampullary lesions (ALs) can be treated by endoscopic (EA) or surgical ampullectomy (SA) or pancreaticoduodenectomy (PD). However, EA carries significant risk of incomplete resection while surgical interventions can lead to substantial morbidity. We performed a systematic review and meta-analysis for R0, adverse-events (AEs) and recurrence between EA, SA and PD. Electronic databases were searched from 1990 to 2018. Outcomes were calculated as pooled means using fixed and random-effects models and the Freeman-Tukey-Double-Arcsine-Proportion-model. We identified 59 independent studies. The pooled R0 rate was 76.6% (71.8–81.4%, I² = 91.38%) for EA, 96.4% (93.6–99.2%, I² = 37.8%) for SA and 98.9% (98.0–99.7%, I² = 0%) for PD. AEs were 24.7% (19.8–29.6%, I² = 86.4%), 28.3% (19.0–37.7%, I² = 76.8%) and 44.7% (37.9–51.4%, I² = 0%), respectively. Recurrences were registered in 13.0% (10.2–15.6%, I² = 91.3%), 9.4% (4.8–14%, I² = 57.3%) and 14.2% (9.5–18.9%, I² = 0%). Differences between proportions were significant in R0 for EA compared to SA (p = 0.007) and PD (p = 0.022). AEs were statistically different only between EA and PD (p = 0.049) and recurrence showed no significance for EA/SA or EA/PD. Our data indicate an increased rate of complete resection in surgical interventions accompanied with a higher risk of complications. However, studies showed various sources of bias, limited quality of data and a significant heterogeneity, particularly in EA studies.

INTRODUCTION: When initial resection of rectal neuroendocrine tumors (r-NETs) is not R0, persistence of local residue could lead to disease recurrence. This study aimed to evaluate the interest of systematic resection of non-R0 r-NET scars. METHODS: Retrospective analysis of all the consecutive endoscopic revisions and resections of the scar after non-R0 resections of r-NETs. RESULTS: A total of 100 patients were included. Salvage endoscopic procedure using endoscopic submucosal dissection or endoscopic full-thickness resection showed an R0 rate of near 100%. Residual r-NET was found in 43% of cases. DISCUSSION: In case of non-R0 resected r-NET, systematic scar resection by endoscopic full-thickness resection or endoscopic submucosal dissection seems necessary.

The incidence of liver metastasis in digestive neuroendocrine tumors is high. Their presence appears as an important prognostic factor in terms of quality of life and survival. These tumors may be symptomatic because of the tumor burden itself and/or the hormonal hyper-secretion induced by the tumor. Surgery is the treatment of choice for resectable tumors and metastasis. Nevertheless, surgery is only possible in a small number of cases. The management of non-resectable liver metastasis is a challenge. The literature is rich but consists predominantly in small retrospective series with a low level of proof. Thus, the choice of one technique over another could be difficult. Local ablative techniques (radiofrequency) or trans-catheter intra-arterial liver-directed treatments (hepatic artery embolization, chemo-embolization, and radio-embolization) are frequently considered for liver metastasis. In the present review, we focus on these different therapeutic approaches in advanced neuroendocrine tumors, results (clinical and radiological), and overall efficacy, and summarize recommendations to help physicians in their clinical practice.

Background: Esophagectomy is recommended after endoscopic resection of an early esophageal cancer when pejorative histoprognostic criteria indicate a high risk of lymph node involvement. Our aim was to analyze the clinical outcomes of a non-surgical, organ preserving management in this clinical setting. Patients and Methods: This retrospective study was performed in two tertiary centers from 2015 to 2020. Patients were included if they had histologically complete resection of an early esophageal cancer, with poor differentiation, lymphovascular invasion or deep submucosal invasion. Endoscopic resection was followed by chemoradiotherapy or follow-up in case of surgical contraindications or patient refusal. Outcome measures were disease-free survival (DFS), overall survival (OS), cancer specific survival (CSS) and toxicity of chemoradiotherapy. Results: Forty-one patients (36 with squamous cell carcinoma and 5 with adenocarcinomas) were included. The estimated high risk of lymph node involvement was based on poor differentiation (10/41; 24%), lympho-vascular invasion (11/41; 27%), muscularis mucosa invasion or deep sub-mucosal invasion (38/41; 93%). Thirteen patients (13/41; 32%) were closely monitored, and 28 (28/41; 68%) were treated by chemoradiotherapy or radiotherapy alone. In the close follow-up group, DFS, OS and CSS were 92%, 92% and 100%, respectively vs. 75%, 79% and 96%, respectively in the chemoradiotherapy group at the end of the follow-up. Serious adverse events related to chemoradiotherapy occurred in 10% of the patients. There were no treatment-related deaths. Conclusions: Our study shows that close follow-up may be an alternative to systematic esophagectomy after endoscopic resection of early esophageal cancer with a predicted high risk of lymph node involvement.

Pancreatic neuroendocrine tumors (p-NETs) are rare tumors with a recent growing incidence. In the 2017 WHO classification, p-NETs are classified into well-differentiated (i.e., p-NETs grade 1 to 3) and poorly differentiated neuroendocrine carcinomas (i.e., p-NECs). P-NETs G1 and G2 are often non-functioning tumors, of which the prognosis depends on the metastatic status. In the localized setting, p-NETs should be surgically managed, as no benefit for adjuvant chemotherapy has been demonstrated. Parenchymal sparing resection, including both duodenum and pancreas, are safe procedures in selected patients with reduced endocrine and exocrine long-term dysfunction. When the p-NET is benign or borderline malignant, this surgical option is associated with low rates of severe postoperative morbidity and in-hospital mortality. This narrative review offers comments, tips, and tricks from reviewing the available literature on these different options in order to clarify their indications. We also sum up the overall current data on p-NETs G1 and G2 management.

Pancreatic ductal adenocarcinoma (PDAC) is a rapidly increasing cause of mortality whose dismal prognosis is mainly due to overwhelming chemoresistance. New therapeutic approaches include physical agents such as ultrasonic cavitation, but clinical applications require further insights in the mechanisms of cytotoxicity. 3-D in vitro culture models such as spheroids exploit realistic spatial, biochemical and cellular heterogeneity that may bridge some of the experimental gap between conventional in vitro and in vivo experiments. To assess the feasibility and efficiency of inertial cavitation associated or not with chemotherapy, in a spheroid model of PDAC. We used DT66066 cells, derived from a genetically-engineered murine PDAC, isolated from KPC-transgenic mice (LSL-Kras^G12D/+; LSL-Trp53^R172H/+; Pdx-1- Cre). Spheroids were obtained by either a standard centrifugation-based method, or by using a magnetic nano-shuttle method allowing the formation of spheroids within 24 hours and facilitating their handling. The spheroids were exposed to ultrasonic inertial cavitation in a specially designed setup. Eight or nine spheroids were analyzed for each of 4 conditions: control, gemcitabine alone, US cavitation alone, US cavitation + gemcitabine. Five US inertial cavitation indexes, corresponding to increased US intensities, were evaluated. The effectiveness of treatment was assessed after 24 hours with the following criteria: spheroid size (growth), ratio of phase S-entered cells (proliferation), proportion of cells in apoptosis or necrosis (mortality). These parameters were assessed by quantitative immunofluorescence techniques. The 3D culture model presented excellent reproducibility. Cavitation induced a significant decrease in the size of spheroids, an effect significantly correlated to an increasing cavitation index (p < 0.0001). The treatment induced cell death whose predominant mechanism was necrosis (p < 0.0001). There was a tendency to a synergistic effect of US cavitation and gemcitabine at 5μM concentration, however significant in only one of the cavitation indexes used (p = 0. 013). Ultrasonic inertial cavitation induced a significant reduction of tumor growth in a spheroid model of PDAC., with necrosis rather than apoptosis as a Cell dominant mechanism of cell death. More investigations are needed to understand the potential role of inertial cavitation in overcoming chemoresistance.