Surgical versus endoscopic gastroenterostomy for gastric outlet obstruction: a retrospective multicentric comparative study of technical and clinical success.

PURPOSE: Gastric outlet obstruction (GOO) is mainly due to advanced malignant disease. GOO can be treated by surgical gastroenterostomy (SGE), endoscopic enteral stenting (EES), or endoscopic ultrasound-guided gastroenterostomy (EUS-GE) to improve the quality of life. METHODS: Between 2009 and 2022, patients undergoing SGE or EUS-GE for GOO were included at three centers. Technical and clinical success rates, post-procedure adverse events (AEs), length of hospital stay (LOS), 30-day all-cause mortality, and recurrence of GOO were retrospectively analyzed and compared between SGE and EUS-GE. Predictive factors for technical and clinical failure after SGE and EUS-GE were identified. RESULTS: Of the 97 patients included, 56 (57.7%) had an EUS-GE and 41 (42.3%) had an SGE for GOO, with 62 (63.9%) GOO due to malignancy and 35 (36.1%) to benign disease. The median follow-up time was 13,4 months (range 1 days-106 months), with no difference between the two groups (p = 0.962). Technical (p = 0.133) and clinical (p = 0.229) success rates, severe morbidity (p = 0.708), 30-day all-cause mortality (p = 0.277) and GOO recurrence (p = 1) were similar. EUS-GE had shorter median procedure duration (p < 0.001), lower post-procedure ileus rate (p < 0.001), and shorter median LOS (p < 0.001) than SGE. In univariate analysis, no risk factors for technical or clinical failure in SGE were identified and abdominal pain reported before the procedure was a risk factor for technical failure in the EUS-GE group. No risk factor for clinical failure was identified for EUS-GE. In the subgroup of GOO due to benign disease, SGE was associated with better technical success (p = 0.035) with no difference in clinical success rate compared to EUS-GE (p = 1). CONCLUSION: EUS-GE provides similar long-lasting symptom relief as SGE for GOO whether for benign or malignant disease. SGE may still be indicated in centers with limited experience with EUS-GE or may be reserved for patients in whom endoscopic technique fails.

The falciform/round ligament "flooring," an effective method to reduce life-threatening post-pancreatectomy hemorrhage occurrence.

PURPOSE: Late post-pancreatectomy hemorrhage (PPH) represents the most severe complication after pancreatic surgery. We have measured the efficacy of major vessels "flooring" with falciform/round ligament to prevent life-threatening grade C late PPH after pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). METHODS: All consecutive patients who underwent PD and DP between 2013 and 2021 were retrospectively reviewed on a prospectively maintained database. The cohort was divided in two groups: "flooring" vs. "no flooring" method group. The "no flooring" group had omental flap interposition. Patient characteristics and operative and postoperative data including clinically relevant postoperative pancreatic fistula (CR-POPF), late PPH (grade B and C), and 90-day mortality were compared between the two groups. RESULTS: Two hundred and forty patients underwent pancreatic resections, including 143 PD and 97 DP. The "flooring" method was performed in 61 patients (39 PD and 22 DP). No difference was found between the two groups concerning severe morbidity, CR-POPF, delayed PPH, and mortality rate. The rate of patients requiring postoperative intensive care unit was lower in the "flooring" than in the "no flooring" method group (11.5% vs. 25.1%, p = 0.030). Among patients with grade B/C late PPH (n = 30), the rate of life-threatening grade C late PPH was lower in the "flooring" than in the "no flooring" method group (28.6% (n = 2/7) vs. 82.6% (n = 19/24), p = 0.014). Risk factor analysis showed that the "flooring" method was the only protective factor against grade C late PPH occurrence (p = 0.013). CONCLUSION: The "flooring" method using the falciform/round ligament should be considered during pancreatectomies to reduce the occurrence of life-threatening grade C late PPH.

Prognostic impact of splenic vessel involvement and tumor size in distal pancreatectomy for adenocarcinoma: a retrospective multicentric cohort study.

PURPOSE: Splenic vessel involvement occurs frequently in pancreatic ductal adenocarcinoma (PDAC) of the body and the tail (B/T) but the impact on survival is unknown. We assessed the influence of radiological and pathologic involvement of splenic artery (p-SA +) and vein (p-SV +) on patient outcomes after distal pancreatectomy (DP) for PDAC. METHODS: From 2013 to 2019, all DP for PDAC in five centers were included. Factors associated with overall (OS) and disease-free (DFS) survival were identified. RESULTS: Among the 76 patients included, 5 (6.6%) had p-SA + only, 11 (14.5%) had p-SV + only, and 24 (31.6%) had both p-SA + and p-SV + . The preoperative CT-scan accuracy to predict p-SV + and p-SA + was high (sensitivity: 91.4% and 82.8%, respectively; negative predictive value: 89.7% and 88.3%, respectively). The 5-year OS and DFS rates were 3.9% and 8.3%, respectively. Multivariate analysis identified splenic vessel involvement (i.e., p-SA + or p-SV + , or both p-SA + and p-SV +) as the only independent factor influencing DFS (HR 4.04; 95% CI [1.22-13.44], p = 0.023). Tumor size ≥ 30 mm was the only independent factor influencing OS (HR 4.04; 95% CI [1.26-12.95], p = 0.019) and was associated with a high risk of p-SA + (p = 0.001) and p-SV + (p < 0.001). CONCLUSION: Tumor size ≥ 30 mm and splenic vessel involvement occurred in more than half of the patients who underwent DP for PDAC and had negative impact on long-term survival. Preoperative CT-scan was reliable to identify splenic vessel involvement in B/T PDAC. Large tumor size and radiological splenic vessel involvement could be taken into account to propose a neoadjuvant treatment.

Delayed post-pancreatectomy hemorrhage and bleeding recurrence after percutaneous endovascular treatment: risk factors from a bi-centric study of 307 consecutive patients.

PURPOSE: Delayed post-pancreatectomy hemorrhage (PPH) is still one of the most dreaded complications after pancreatic surgery. Its management is now focused on percutaneous endovascular treatments (PETs). METHODS: Between 2013 and 2019, 307 patients underwent pancreatic resection. The first endpoint of this study was to determine predictive factors of delayed PPH. The second endpoint was to describe the management of intra-abdominal abscesses (IAA). The third endpoint was to identify risk factors of bleeding recurrence after PET. Patients were divided into two cohorts: A retrospective analysis was performed ("cohort 1," "learning set") to highlight predictive factors of delayed PPH. Then, we validated it on a prospective maintained cohort, analyzed retrospectively ("cohort 2," "validation set"). Second and third endpoints studies were made on the entire cohort. RESULTS: In cohort 1, including 180 patients, 24 experienced delayed PPH. Multivariate analysis revealed that POPF diagnosis on postoperative day (POD) 3 (p=0.004) and IAA (p=0.001) were independent predictive factors of delayed PPH. In cohort 2, association of POPF diagnosis on POD 3 and IAA was strongly associated with delayed PPH (area under the curve [AUC] 0.80; 95% confidence interval [CI] [0.59-0.94]; p=0.003). Concerning our second endpoint, delayed PPH occurred less frequently in patients who underwent postoperative drainage procedure than in patients without IAA drainage (p=0.002). Concerning our third endpoint, a higher body mass index (BMI) (p=0.027), occurrence of postoperative IAA (p=0.030), and undrained IAA (p=0.011) were associated with bleeding recurrence after the first PET procedure. CONCLUSION: POPF diagnosis on POD 3 and intra-abdominal abscesses are independent predictive factors of delayed PPH. Therefore, patients presenting an insufficiently drained POPF leading to intra-abdominal abscess after pancreatic surgery should be considered as a high-risk situation of delayed PPH. High BMI, occurrence of postoperative IAA, and undrained IAA were associated with recurrence of bleeding after PET.

Prospective study on predictability of complications by pancreatic surgeons.

PURPOSE: We evaluated the intuition of expert pancreatic surgeons, in predicting the associated risk of pancreatic resection and compared this "intuition" to actual operative follow-up. The objective was to avoid major complications following pancreatic resection, which remains a challenge. METHODS: From January 2015 to February 2018, all patients who were 18 years old or more undergoing a pancreatic resection (pancreaticoduodenectomy [PD], distal pancreatectomy [DP], or central pancreatectomy [CP]) for pancreatic lesions were included. Preoperatively and postoperatively, all surgeons completed a form assessing the expected potential occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF: grade B or C), postoperative hemorrhage, and length of stay. RESULTS: Preoperative intuition was assessed for 101 patients for 52 PD, 44 DP, and 5 CP cases. Overall mortality and morbidity rates were 6.9% (n = 7) and 67.3% (n = 68), respectively, and 38 patients (37.6%) developed a POPF, including 27 (26.7%) CR-POPF. Concordance between preoperative intuition of CR-POPF occurrence and reality was minimal, with a Cohen's kappa coefficient (κ) of 0.175 (P value = 0.009), and the same result was obtained between postoperative intuition and reality (κ = 0.351; P < 0.001). When the pancreatic parenchyma was hard, surgeons predicted the absence of CR-POPF with a negative predictive value of 91.3%. However, they were not able to predict the occurrence of CR-POPF when the pancreas was soft (positive predictive value 48%). CONCLUSIONS: This study assessed for the first time the surgeon's intuition in pancreatic surgery, and demonstrated that pancreatic surgeons cannot accurately assess outcomes except when the pancreatic parenchyma is hard.

Preoperative Biliary Stenting and Major Morbidity After Pancreatoduodenectomy: Does Elapsed Time Matter?: The FRAGERITA Study Group.

OBJECTIVE: To analyze possible associations between the duration of stent placement before surgery and the occurrence and severity of postoperative complications after pancreatoduodenectomy (PD). BACKGROUND: The effect of preoperative stent duration on postoperative outcomes after PD has not been investigated. METHODS: From 2013 to 2016, patients who underwent PD for any reasons after biliary stent placement at 5 European academic centers were analyzed from prospectively maintained databases. The primary aim was to investigate the association between the duration of preoperative biliary stenting and postoperative morbidity. Patients were stratified by stent duration into 3 groups: short (<4 weeks), intermediate (4-8 weeks), and long (≥8 weeks). RESULTS: In all, 312 patients were analyzed. The median time from stent placement to surgery was 37 days (2-559 days), and most operations were performed for pancreatic cancer (67.6%). Morbidity and mortality rates were 56.0% and 2.6%, respectively. Patients in the short group (n = 106) experienced a higher rate of major morbidity (43.4% vs 20.0% vs 24.2%; P < 0.001), biliary fistulae (13.2% vs 4.3% vs 5.5%; P = 0.031), and length of hospital stay [16 (10-52) days vs 12 (8-35) days vs 12 (8-43) days; P = 0.025]. A multivariate adjusted model identified the short stent duration as an independent risk factor for major complications (odds ratio 2.64, 95% confidence interval 1.23-5.67, P = 0.013). CONCLUSIONS: When jaundice treatment cannot be avoided, delaying surgery up to 1 month after biliary stenting may reduce major morbidity, procedure-related complications, and length of hospital stay.

A 25-gene classifier predicts overall survival in resectable pancreatic cancer.

BACKGROUND: Pancreatic carcinoma is one of the most lethal human cancers. In patients with resectable tumors, surgery followed by adjuvant chemotherapy is the only curative treatment. However, the 5-year survival is 20%. Because of a strong metastatic propensity, neoadjuvant chemotherapy is being tested in randomized clinical trials. In this context, improving the selection of patients for immediate surgery or neoadjuvant chemotherapy is crucial, and high-throughput molecular analyses may help; the present study aims to address this. METHODS: Clinicopathological and gene expression data of 695 pancreatic carcinoma samples were collected from nine datasets and supervised analysis was applied to search for a gene expression signature predictive for overall survival (OS) in the 601 informative operated patients. The signature was identified in a learning set of patients and tested for its robustness in a large independent validation set. RESULTS: Supervised analysis identified 1400 genes differentially expressed between two selected patient groups in the learning set, namely 17 long-term survivors (LTS; ≥ 36 months after surgery) and 22 short-term survivors (STS; dead of disease between 2 and 6 months after surgery). From these, a 25-gene prognostic classifier was developed, which identified two classes ("STS-like" and "LTS-like") in the independent validation set (n = 562), with a 25% (95% CI 18-33) and 48% (95% CI 42-54) 2-year OS (P = 4.33 × 10-9), respectively. Importantly, the prognostic value of this classifier was independent from both clinicopathological prognostic features and molecular subtypes in multivariate analysis, and existed in each of the nine datasets separately. The generation of 100,000 random gene signatures by a resampling scheme showed the non-random nature of our prognostic classifier. CONCLUSION: This study, the largest prognostic study of gene expression profiles in pancreatic carcinoma, reports a 25-gene signature associated with post-operative OS independently of classical factors and molecular subtypes. This classifier may help select patients with resectable disease for either immediate surgery (the LTS-like class) or neoadjuvant chemotherapy (the STS-like class). Its assessment in the current prospective trials of adjuvant and neoadjuvant chemotherapy trials is warranted, as well as the functional analysis of the classifier genes, which may provide new therapeutic targets.

Comparison of different feeding regimes after pancreatoduodenectomy - a retrospective cohort analysis.

BACKGROUND: Delayed gastric emptying (DGE) is the most frequent pancreatic specific complication (PSC) after pancreaticoduodenectomy (PD). Several gastric decompression systems exist to manage DGE. Patients with a pancreatic tumor require prolonged nutrition; however, controversies exist concerning nutrition protocol after PD. The aim of the study was to assess the safety and efficacy of nasogastric (NG), gastrostomy (GT), and gastrojejunostomy (GJ) tubes with different feeding systems on postoperative courses. METHODS: Between January 2013 and March 2016, 86 patients underwent PD with pancreaticogastrostomy. Patients were divided into three groups: GJ group with enteral nutrition (EN, n = 12, 14%), NG (n = 31, 36%) and GT groups (n = 43, 50%), both with total parenteral nutrition (TPN). RESULTS: Patients in the GJ (n = 9, 75%) and GT (n = 18, 42%) groups had an American Society of Anesthesiologists (ASA) score of 3 more often than those in the NG group (n = 5, 16%, p ≤ 0.01). Multivariate analysis identified the GT tube with TPN as an independent risk factor of severe morbidity (p = 0.02) and DGE (p < 0.01). An ASA score of 3, jaundice, common pancreatic duct size ≤3 mm and soft pancreatic gland texture (p < 0.05) were found as independent risk factors of PSCs. Use of a GJ tube with EN, GT tube with TPN, jaundice, and PSCs were identified as independent risk factors for greater postoperative length of hospital stay (p < 0.01). Mean global hospitalization cost did not differ between groups. CONCLUSION: GT tube insertion with TPN was associated with increased severe postoperative morbidity and DGE and should not be recommended. EN through a GJ tube after PD is feasible but does not have clear advantages on postoperative courses compared to an NG tube.

Predictive factors of severe complications for ampullary, bile duct and duodenal cancers following pancreaticoduodenectomy: Multivariate analysis of a 10-year multicentre retrospective series.

BACKGROUND: Postoperative outcomes following pancreaticoduodenectomy are well described for pancreatic cancers. Due to a lower incidence rate, complication rates and relative predictive factors are less detailed for ampullary, bile duct and duodenal cancers. METHODS: Medical charts of patients operated on between 2001 and 2011 for an ampullary, bile duct or duodenal cancer were reviewed. Data were retrospectively studied with respect to demographics, surgical management, postoperative complications and histological findings. Specific complication rates were reported, and predictive factors for severe morbidity and mortality were determined by multivariate analysis. RESULTS: 135 patients were identified: 55 ampullary, 55 bile duct and 25 duodenal cancers. Twelve patients (8.9%) deceased postoperatively, and 36 others (26.7%) presented severe complications. Sixty-seven percent of the pancreas was soft, and pancreatic hardness was found to be the main protective factor against severe morbidity (HR = 0.36, 95% CI = 0.14-0.94, P = 0.037). Age and postpancreatectomy haemorrhage were independent predictors for death (HR = 14.63, 95% CI = 1.57-135.77, P = 0.018, and HR = 14.71, 95% CI = 2.86-75.62, P = 0.001, respectively). Only the use of an external transanastomotic duct stent significantly reduced both the morbidity (HR = 0.37, 95% CI = 0.16-0.83, P = 0.016), and the mortality (HR = 0.12, 95% CI = 0.02-0.69, P = 0.017). CONCLUSIONS: Pancreaticoduodenectomy for ampullary, bile duct and duodenal cancers is a high-risk procedure. The systematic use of transanastomotic duct stents would significantly decrease the complication rate. Older patients should beneficiate from specific preoperative evaluation using an adapted index. Omental flap techniques to prevent a postpancreatectomy haemorrhage should be efficient. Effects of preoperative octreotid to harden the pancreas should be clarified.

Transcriptomic analysis predicts survival and sensitivity to anticancer drugs of patients with a pancreatic adenocarcinoma.

A major impediment to the effective treatment of patients with pancreatic ductal adenocarcinoma (PDAC) is the molecular heterogeneity of this disease, which is reflected in an equally diverse pattern of clinical outcome and in responses to therapies. We developed an efficient strategy in which PDAC samples from 17 consecutive patients were collected by endoscopic ultrasound-guided fine-needle aspiration or surgery and were preserved as breathing tumors by xenografting and as a primary culture of epithelial cells. Transcriptomic analysis was performed from breathing tumors by an Affymetrix approach. We observed significant heterogeneity in the RNA expression profile of tumors. However, the bioinformatic analysis of these data was able to discriminate between patients with long- and short-term survival corresponding to patients with moderately or poorly differentiated PDAC tumors, respectively. Primary culture of cells allowed us to analyze their relative sensitivity to anticancer drugs in vitro using a chemogram, similar to the antibiogram for microorganisms, establishing an individual profile of drug sensitivity. As expected, the response was patient dependent. We also found that transcriptomic analysis predicts the sensitivity of cells to the five anticancer drugs most frequently used to treat patients with PDAC. In conclusion, using this approach, we found that transcriptomic analysis could predict the sensitivity to anticancer drugs and the clinical outcome of patients with PDAC.

Portal Vein Stent Placement in Five Patients with Chronic Portal Vein Thrombosis Prior to Pancreatic Surgery.

Five patients with pancreatic tumors and chronic portal vein (PV) thrombosis underwent PV stent placement before surgery. The patients either had resectable tumors or locally advanced tumors with stable, partial, or complete response to neoadjuvant therapy. PV stent placement removed periportal collaterals in all cases, with no complications, in a mean time of 150 minutes. Patients received a daily dose of subcutaneous low-molecular-weight heparin until 12 hours before surgery, and low-molecular-weight heparin was resumed for 30 days after surgery. Surgery was performed 1 day to 3 months after PV stent placement, with no complications related to periportal collaterals.

Surgical management of advanced pancreatic neuroendocrine tumors: short-term and long-term results from an international multi-institutional study.

BACKGROUND: The role of extended resections in the management of advanced pancreatic neuroendocrine tumors (PNETs) is not well defined. METHODS: Between 1995 and 2012, 134 patients with PNET underwent isolated (isoPNET group: 91 patients) or extended pancreatic resection (synchronous liver metastases and/or adjacent organs) (advPNET group: 43 patients). RESULTS: The associated resections included 27 hepatectomies, 9 vascular resections, 12 colectomies, 10 gastrectomies, 4 nephrectomies, 4 adrenalectomies, and 3 duodenojejunal resections. R0 was achieved in 41 patients (95%) in the advPNET. The rates of T3-T4 (73 vs 16%; p < .0001) and N+ (35 vs 13%; p = .007) were higher in the advPNET group. Mortality (5 vs 2%) and major morbidity (21 vs 19%) rates were similar between the 2 groups. The 5-year overall survival (OS) of the series was 87% in the isoPNET group and 66% in the advPNET group (p = .006). Only patients with both locally advanced disease and liver metastases showed worse survival (p = .0003). The advPNET group developed recurrence earlier [disease-free survival (DFS) at 5 years: 26 vs 81%; p < .001]. In univariate analysis, negative prognostic factors of survival were: poor degree of differentiation (p < .001), liver metastasis (p = .011), NE carcinoma (p < .001), and resection of adjacent organs (p = .013). The multivariate analysis did not highlight any factor that influenced OS. In multivariate analysis independent DFS factors were a poor degree of differentiation (p = .03) and the European Neuroendocrine Tumor Society stage (p = .01). CONCLUSIONS: An aggressive surgical approach for locally advanced or metastatic tumors is safe and offers long-term survival.

Pancreatic cancer-induced cachexia is Jak2-dependent in mice.

Cancer cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and it is one of the most frequent causes of death. Severe wasting accounts for more than 80% in patients with advanced pancreatic cancer. Here we wanted to define, by using an microarray approach and the Pdx1-cre;LSL-Kras(G12D) ;INK4a/arf(fl/fl) mice model, the pathways involved in muscle, liver, and white adipose tissue wasting. These mice, which develop systematically pancreatic cancer, successfully reproduced many human symptoms afflicted with this disease, and particularly cachexia. Using the profiling analysis of pancreatic cancer-dependent cachectic tissues we found that Jak2/Stat3 pathways, p53 and NFkB results activated. Thus, our interest was focused on the Jak2 pathways because it is pharmacologically targetable with low toxicity and FDA approved drugs are available. Therefore, Pdx1-cre;LSL-Kras(G12D) ;INK4a/arf(fl/fl) mice were treated with the Jak2 inhibitor AG490 compound daily starting at 7 weeks old and for a period of 3 weeks and animals were sacrificed at 10 weeks old. Body weight for control mice was 27.84 ± 2.14 g, for untreated Pdx1-cre;LSL-Kras(G12D) ;INK4a/arf(fl/fl) was 14.97 ± 1.99 g, whereas in animals treated with the AG490 compound the weight loss was significantly less to 24.53 ± 2.04 g. Treatment with AG490 compound was efficient since phosphorylation of Jak2 and circulating interleukin-6 (IL6) levels were significantly reduced in cachectic tissues and in mice respectively. In conclusion, we found that Jak2/Stat3-dependent intracellular pathway plays an essential role since its pharmacological inhibition strongly attenuates cachexia progression in a lethal transgenic pancreatic cancer model.

Biliary complications after pancreaticoduodenectomy: skinny bile ducts are surgeons' enemies.

BACKGROUND: The aim of this study was to determine the incidence and predisposing factors of biliary complications (BCs) after pancreaticoduodenectomy (PD) and report our experience in managing these BCs. Pancreatic surgery, particularly PD, has benefited from improvements in operative techniques and postoperative care and is currently safer in terms of mortality. However, the morbidity associated with PD remains high, including frequent complications such as delayed gastric emptying and pancreatic fistulas. Rarer but important BCs are those that manifest as bile leaks (BLs) and biliary strictures (BSs). METHODS: Between April 2005 and December 2011, a total of 397 patients underwent PD at two centers. All data were retrospectively studied with respect to age, gender, pancreatic pathology, neoadjuvant treatment, preoperative biliary stenting, intraoperative data, postoperative pancreatic fistula, BL and BS rates, and mortality. The management of BCs was also analyzed. RESULTS: Thirty patients experienced a BC: 13 BLs (3.3 %) and 17 BSs (4.3 %). A thin bile duct (<5 mm), measured during surgery, was the only predisposing factor for developing a BL or a BS. The management of the BLs consisted of surveillance in six patients (46 %), percutaneous drainage of bilioma in four patients (31 %), and reintervention in three patients (23 %). No patient with a BS had surgery as the frontline treatment: the initial management consisted of an endoscopic procedure, a percutaneous procedure, or medical treatment. Four patients (23.5 %) underwent surgical treatment after failure of nonsurgical procedures. CONCLUSIONS: The only identified predictive factor of BC, either a BS or a BL, was a thin bile duct. Although the noninvasive technique was the treatment of choice initially, reintervention was required in almost 25 % of the cases.

Novel role of VMP1 as modifier of the pancreatic tumor cell response to chemotherapeutic drugs.

We hypothesized that inhibiting molecules that mediate the adaptation response to cellular stress can antagonize the resistance of pancreatic cancer cells to chemotherapeutic drugs. Toward this end, here, we investigated how VMP1, a stress-induced autophagy-associated protein, modulate stress responses triggered by chemotherapeutic agents in PDAC. We find that VMP1 is particularly over-expressed in poorly differentiated human pancreatic cancer. Pharmacological studies show that drugs that work, in part, via the endoplasmic reticulum stress response, induce VMP1 expression. Similarly, VMP1 is induced by known endoplasmic reticulum stress activators. Genetic inactivation of VMP1 using RNAi-based antagonize the pancreatic cancer stress response to antitumoral agents. Functionally, we find that VMP1 regulates both autophagy and chemotherapeutic resistance even in the presence of chloroquin, ATG5 or Beclin 1 siRNAs, or a Beclin 1-binding VMP1 mutant. In addition, VMP1 modulates endoplasmic reticulum stress independently of its coupling to the molecular and cellular autophagy machinery. Preclinical studies demonstrate that xenografts expressing an inducible and tractable form of VMP1 show increased resistance to the gemcitabine treatment. These results underscore a novel role for VMP1 as a potential therapeutic target for combinatorial therapies aimed at sensitizing pancreatic cancer cells to chemotherapeutic agents as well as provide novel molecular mechanisms to better understand this phenomenon.

Laparoscopic approach is feasible in Crohn's complex enterovisceral fistulas: a case-match review.

BACKGROUND: Complex enterovisceral fistulas are internal fistulas joining a "diseased" organ to any intra-abdominal "victim" organ, with the exception of ileoileal fistulas. Few publications have addressed laparoscopic surgery for complex fistulas in Crohn's disease. OBJECTIVE: The aim of this study was to evaluate the feasibility of such an approach. DESIGN: This study is a retrospective, case-match review. SETTINGS: This study was conducted at a tertiary academic hospital. PATIENTS: : All patients who underwent a laparoscopic ileocecal resection for complex enterovisceral fistulas between January 2004 and August 2011 were included. They were matched to a control group undergoing operation for nonfistulizing Crohn's disease according to age, sex, nutritional state, preoperative use of steroids, and type of resection performed. Matching was performed blind to the peri- and postoperative results of each patient. MAIN OUTCOME MEASURES: The 2 groups were compared in terms of operative time, conversion to open surgery, morbidity and mortality rates, and length of stay. RESULTS: Eleven patients presenting with 13 complex fistulas were included and matched with 22 controls. Group 1 contained 5 ileosigmoid fistulas (38%), 3 ileotransverse fistulas (23%), 3 ileovesical fistulas (23%), 1 colocolic fistula (8%), and 1 ileosalpingeal fistula (8%). There were no significant differences between the groups in terms of operative time (120 (range, 75-270) vs 120 (range, 50-160) minutes, p = 0.65), conversion to open surgery (9% vs 0%, p = 0.33), stoma creation (9% vs 14%, p = 1), global postoperative morbidity (18% vs 32%, p = 0.68), and major complications (Dindo III: 0% vs 9%, p = 0.54; Dindo IV: 0% vs 0%, p = 1), as well as in terms of length of stay (8 (range, 7-32) vs 9 (range, 5-17) days, p = 0.72). No patients died. LIMITATIONS: This is a retrospective review with a small sample size. CONCLUSION: A laparoscopic approach for complex fistulas is feasible in Crohn's disease, with outcomes similar to those reported for nonfistulizing forms.

Endovascular management of severe bleeding after major abdominal surgery.

BACKGROUND: In this study we analyzed embolization and stent-graft results. METHODS: Demographics, indications, procedures, and outcomes of patients treated with embolization or stent grafting for late postoperative bleeding after major abdominal surgery were retrospectively recorded. Outcomes were analyzed on an intention-to-treat basis. RESULTS: Between 2004 and 2008, 14 consecutive patients (11 men and 3 women, mean age 64 years) were treated for hemorrhage responsible for shock in 6 patients (43%), occurring after pancreaticoduodenectomy (n=13) or subtotal gastrectomy (n=1). Mean onset occurred at 23 days postoperatively (range 7-75 days). Bleeding site included: the stump of the gastroduodenal artery (n=10), splenic artery (n=2), common hepatic artery (n=1), and right gastric artery (n=1). Initial success was obtained in 13 patients (93%); the only failure of stent-graft deployment required re-laparotomy. Treatment included embolization in 8 patients and stent grafting in 5 patients. In the embolization group, 5 complications (62%) occurred: 4 rebleeding and 1 gastric perforation, compared with no early complications in the stent-graft group. One patient died in each group. The mean follow-up was 25 months (range 6-57 months). CONCLUSIONS: Stent grafting seems to provide definitive hemostasis and fewer complications compared with embolization.

Intra-pancreatic distal cholangiocarcinoma and pancreatic ductal adenocarcinoma: a common short and long-term prognosis?

The aim of the study was to compare histological features, postoperative outcomes, and long-term prognostic factors after pancreaticoduodenectomy for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma. From 2005 to 2017, 188 pancreaticoduodenectomies (pancreatic ductal adenocarcinoma n = 151, distal cholangiocarcinoma n = 37) were included. Postoperative outcomes were compared after matching on pancreatic gland texture and main pancreatic duct size. Matching according to tumor size, lymph node invasion and resection margin was used to compare overall and disease-free survival. Distal cholangiocarcinoma patients had more often "soft" pancreatic gland (P = 0.002) and small size main pancreatic duct (P = 0.001). Pancreatic ductal adenocarcinoma patients had larger tumors (P = 0.009), and higher lymph node ratio (P = 0.017). Severe morbidity (P = 0.023) and clinically relevant pancreatic fistula (P = 0.018) were higher in distal cholangiocarcinoma patients. After matching on gland texture and main pancreatic duct diameter, clinically relevant postoperative pancreatic fistula was still more frequent in distal cholangiocarcinoma patients (P = 0.007). Tumor size > 20 mm was predictive of impaired overall survival (P = 0.024) and disease-free survival (P = 0.003), tumor differentiation (P = 0.027) was predictive of impaired overall survival. Survival outcomes for distal cholangiocarcinoma and pancreatic ductal cholangiocarcinoma were similar after matching patients according to tumor size, lymph node invasion and resection margin. Long-term outcomes after pancreaticoduodenectomy for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma patients are similar. Postoperative course is more complicated after pancreaticoduodenectomy for distal cholangiocarcinoma than pancreatic ductal adenocarcinoma. After pancreaticoduodenectomy, patients with distal cholangiocarcinoma and pancreatic ductal adenocarcinoma have similar long-term oncological outcomes.

Postoperative day 1 combination of serum C-reactive protein and drain amylase values predicts risks of clinically relevant pancreatic fistula. The "90-1000" score.

BACKGROUND: Several scoring systems predict risks of clinically relevant postoperative pancreatic fistula after pancreatectomy, but none have emerged as the gold standard. This study aimed to evaluate the accuracy of postoperative day 1 drain amylase and serum C-reactive protein levels in predicting clinically relevant postoperative pancreatic fistula compared with intraoperative pancreatic characteristics. METHODS: Patients who underwent pancreatectomy between 2017 and 2019 were included prospectively. Cutoff values were determined using receiver operating characteristic curves, and a score combining postoperative day 1 drain amylase and serum C-reactive protein was tested in a multivariate logistic regression model to evaluate clinically relevant postoperative pancreatic fistula risk. RESULTS: A total of 274 pancreatic resections (182 pancreaticoduodenectomies and 92 distal pancreatectomies) were included. The pancreatic gland texture was "soft" in 47.8% (n = 131), and 55.8% (n = 153) had a small size main pancreatic duct (≤3 mm). Clinically relevant postoperative pancreatic fistula occurred in 58 patients (21.2%). Drain amylase ≥1,000 UI/L and serum C-reactive protein ≥90 mg/L were identified as the optimal cutoffs to predict clinically relevant postoperative pancreatic fistula. On multivariate analysis these cutoffs were independent predictors of clinically relevant postoperative pancreatic fistula after both pancreaticoduodenectomies (drain amylase: P < .001, serum C-reactive protein: P = .006) and distal pancreatectomies (drain amylase: P = .009, serum C-reactive protein: P = .001). The postoperative day 1 "90-1000" model, a 2-value score relying on these cutoffs, significantly (P < .001) outperformed intraoperative pancreatic parenchymal characteristics in predicting clinically relevant postoperative pancreatic fistula after both pancreaticoduodenectomies and distal pancreatectomies. A postoperative day 1 "90-1000" score = 0 had a negative predictive value of 97% and 94%, respectively, after pancreaticoduodenectomy and distal pancreatectomies. CONCLUSION: A combined score relying on postoperative day 1 values of drain amylase and serum C-reactive protein levels was accurate in predicting risks of clinically relevant postoperative pancreatic fistula after pancreatectomy.

Surgery of small bowel melanoma metastases in the era of efficient medical therapies: a retrospective cohort study.

Surgery of small bowel melanoma metastases has to be reconsidered in the era of targeted treatments and immunotherapy. To retrospectively assess context and outcomes of small bowel melanoma metastases resections. All consecutive melanoma patients who underwent resection of small bowel metastases between 2011 and 2017, in a single referral center, were retrospectively analyzed through melanoma-specific survival (MSS). A total of 20 patients were included with a 47.8 months median follow-up. Before small bowel surgery, eight patients (40%) were asymptomatic while seven had anemia and five patients had abdominal pain. All resections were decided on tumor boards except for three surgeries performed in the emergency setting. In the whole cohort, MSS was 89.5 months with 50% of patients alive at the study endpoint. We classified surgical indications in three groups: (1) surgery as a pivotal treatment for mono- or oligo-metastases limited to the small bowel (n = 6); (2) salvage surgery for symptomatic patients in order to preserve their chances to switch to an active line of medical treatment (n = 8); and (3) surgery of small bowel dissociated metastatic progression for patients otherwise controlled (n = 6), aiming at keeping patients with the same treatment or active follow-up. In these three situations, the objective of surgery was usually met, and most patients had a long median MSS after surgery: 70.3 months, 89.5 months and 72.4 months, respectively. Although medical treatments have dramatically improved survival in metastatic melanoma, surgical control of life-threatening localization like small bowel metastases is often a condition for long survival.