Endoscopic internal drainage for the management of leak, fistula, and collection after sleeve gastrectomy: our experience in 617 consecutive patients.

BACKGROUND: Endoscopy plays a pivotal role in the management of adverse events (AE) following bariatric surgery. Leaks, fistulae, and post-operative collection after sleeve gastrectomy (SG) may occur in up to 10% of cases. OBJECTIVES: To evaluate the efficacy and safety of endoscopic internal drainage (EID) for the management of leak, fistula, and collection following SG. SETTING: Retrospective, observational, single center study on patients referred from several bariatric surgery departments to an endoscopic referral center. METHODS: EID was used as first-line treatment for the management of leaks, fistulae, and collections. Leaks and fistulae were treated with double pigtail stent (DPS) deployment in order to guarantee internal drainage and second intention cavity obliteration. Collections were treated with endoscropic ultrasound (EUS)-guided deployment of DPS or lumen apposing metal stents. RESULTS: A total of 617 patients (83.3% female; mean age, 43.1 yr) were enrolled in the study for leak (n = 300, 48.6%), fistula (n = 285, 46.2%), and collection (n = 32, 5.2%). Median follow-up was 19.5 months. Overall clinical success was 84.7% whereas 15.3% of cases required revisional surgery after EID failure. Clinical success according to type of AE was 89.5%, 78.5%, and 90% for leak, fistula, and collection, respectively. A total of 10 of 547 (1.8%) presented a recurrence during follow-up. A total of 28 (4.5%) AE related to the endoscopic treatment occurred. At univariate logistic regression predictors of failure were: fistula (OR 2.012), combined endoscopic approach (OR 2.319), need for emergency surgery (OR 1.755), and previous endoscopic treatment (OR 4.818). CONCLUSION: Early EID for the management of leak, fistula, and post-operative collection after SG seems a safe and effective first-line approach with good long-term results.

Thoracoscopic removal of mediastinal parathyroid glands: a critical appraisal of an emerging technique.

OBJECTIVE: To retrospectively evaluate the feasibility of thoracoscopic removal of mediastinal parathyroids. SUMMARY BACKGROUND DATA: Mediastinal exploration to resect ectopic parathyroid(s) is needed in approximately 2% of cases in hyperparathyroidism. Recent advances in thoracoscopic surgery allow for a minimally invasive treatment. METHODS: From 1999 through 2007, 13 patients affected by primary hyperparathyroidism (11 females, mean age 60 years, range: 22-88) underwent thoracoscopic removal of mediastinal parathyroids. Scintigraphy produced positive results in 11 of 13 cases, computed tomography scan in 9 of 10, parathyroid hormone venous sampling in 10 of 10 patients, and magnetic resonance imaging in 5 of 7. Right thoracoscopic access was used in 9 patients, left in 4. Postoperative outcome was analyzed. RESULTS: Thoracoscopy enabled retrieval of mediastinal parathyroids in 10 of 13 (78%) cases. Mean operating time was 92 minutes (range: 50-240). One procedure (8%) was converted. No perioperative deaths/major complications occurred. Mild complications occurred in 2 of 13 (15%) patients (pneumothorax/pneumonia, transient recurrent nerve palsy). Mean hospital stay was 4.7 days (range: 2-15). At a mean follow-up of 73 months (range: 16-105), parathyroid hormone and calcium venous concentrations were high in 3 patients. Unsuccessful procedures were related to doubtful or non-concordant preoperative localization. CONCLUSIONS: The thoracoscopic approach for mediastinal parathyroidectomy is feasible and safe. An accurate preoperative work-up should be standardized to avoid useless procedures. In case of negative preoperative localization of the abnormal gland, thoracoscopy should not be adopted as a diagnostic tool.

Cholecystocolonic fistula: facts and myths. A review of the 231 published cases.

BACKGROUND: Cholecystocolonic fistula (CCF) is the second most common cholecystoenteric fistula and is often discovered intraoperatively, resulting in a challenging situation for the surgeon, who is forced to switch to a complex procedure, often in old, unfit patients. Management of this uncommon but possible finding is still ill defined. METHODS: An extensive review of 160 articles published from 1950 to 2006 concerning 231 cases of CCF was performed. RESULTS: CCF is mostly an affliction of women in their sixth to seventh decades and is rarely diagnosed preoperatively. Chronic diarrhea is the key symptom in nonemergency patients, but, in one-fourth of cases, CCF presents with an acute onset, mostly biliary ileus. In one-fourth of patients, a second hepatobiliary abnormality is present, including gallbladder cancer in 2% of cases. In uncomplicated cases, diverting colostomy is not performed anymore, and laparoscopy treatment has been described in specialized centers. Symptomatic treatment of concomitant biliary ileus (without treating CCF) is a feasible option. Resolution of colonic biliary ileus by interventional endoscopy is reported. CONCLUSION: CCF should be considered in differential diagnosis of diarrhea, especially in old, female patients. A possible second hepatobiliary abnormality should be always investigated. Extemporaneous frozen section should be performed if gallbladder cancer is suspected. Depending on clinical presentation, different treatments for CCF are indicated, ranging from minimally invasive procedures to extensive resection.

Early strangulated recurrence of incisional hernia after laparoscopic repair: an old complication for a new technique.

The introduction of laparoscopy in incisional hernia repair is giving rise to a new class of complications, specific of new techniques and materials. A case of early failure of incisional hernia laparoscopic repair complicated by the strangulation of a jejunal loop four months after surgery is reported. The use of inappropriate material (tacks) to fix the prosthesis to the abdominal wall, a sudden increase of intra-abdominal pressure caused by an episode of haematemesis four hours postoperatively (associated to its consequent endoscopic treatment), and the formation of rectus abdominis muscle hematoma are reported as the main factors determining the slippage of the mesh from the correct position and, ultimately, the early failure of the ventral hernia repair. Furthermore, the aetiology of early failure of laparoscopic incisional hernia repair, reported in literature, is reviewed.

Complete hepatocellular carcinoma necrosis following sequential porto-arterial embolization.

Most patients with hepatocellular carcinoma (HCC) are not eligible for curative treatment, which is resection or transplantation. Two recent series have emphasized the potential benefits of preoperative arterio-portal embolization prior to surgical resection of such tumours. This preoperative strategy offers a better disease free survival rate and a higher rate of total tumor necrosis. In case of non resectable HCC it is now widely accepted that transarterial chemoembolization (TACE) leads to a better survival when compared to conservative treatment. Thus, the question remains whether combined portal vein embolization (PVE) may enhance the proven efficiency of TACE in patients with unresectable HCC. We herein report the case of a 56-year-old cirrhotic woman with a voluminous HCC unsuitable for surgical resection. Yet, complete tumour necrosis and prolonged survival could be achieved after a combined porto-arterial embolization. This case emphasizes the potential synergistic effect of a combined arterio-portal embolization and the hypothetical survival benefit of such a procedure, in selected patients, with HCC not suitable for surgery or local ablative therapy.

Laparoscopic diagnosis and treatment of primary torsion of the greater omentum.

Clinical presentation of primary torsion of the greater omentum is nonspecific, thus rarely allowing for a preoperative diagnosis. Three patients presented with acute but nonspecific abdominal symptoms. Because ultrasonographic and radiologic findings were unclear, all patients underwent diagnostic laparoscopy. In all cases, laparoscopy enabled us to achieve the diagnosis and to perform a resection of necrotic omentum. The mean duration of the procedure was 56 minutes (range: 42 to 76). The postoperative course was uneventful and the patients were discharged on postoperative day 1 (2) and 3. The value of diagnostic laparoscopy increases when the disease can be treated laparoscopically. The laparoscopic vision allowed us to explore the whole peritoneal cavity, so achieving the diagnosis, and to place the operative trocars at the most convenient sites. The laparoscopic resection of the greater omentum is an easy task even for inexperienced laparoscopic surgeons, allowing patients to benefit from the advantages of a mini-invasive approach.

EUS-Guided Transrectal Evacuation of Organized Pelvic Collection Following Roux-en-Y Gastric Bypass After Failure of Radiological and Surgical Approach.

INTRODUCTION: Postoperative collections are an important cause of morbidity following obesity surgery. Surgical revision is most often required if general sepsis is present. Conservative treatment consists of broad spectrum antibiotics and percutaneous drainage of any collection. EUS drainage is a new technique that is gaining momentum allowing an easy access to collections close to the GI tract. MATERIALS AND METHODS: We present the case report of a 39-year-old woman who underwent to robotic Roux-en-Y gastric bypass for morbid obesity. She developed a jejuno-jejunal dehiscence treated with revision surgery. Afterward, a pelvic collection/hematoma was highlighted; however, neither percutaneous approach nor surgery succeeded in draining it. RESULTS: EUS-guided deployment of a fully covered lumen-apposing metal stent was performed. Subsequently, two necrosectomies were required to remove necrotic tissue and clots from the perirectal cavity. Finally, three double pigtail stents were deployed to promote healing. The patient spontaneously expelled the stents with the stool, and she is asymptomatic after a follow-up of 3 months. CONCLUSION: EUS transmural rectal drainage may represent a sound option for the treatment of pelvic postoperative collections. FCLAMS deployment guarantees a rapid drainage allowing to perform an endoscopic necrosectomy.

The role of intraoperative angiography in arterial thromboembolectomy for non-traumatic acute upper limb ischaemia.

The aim of the study was to investigate the influence of intraoperative arteriography on the outcome of upper limb acute arterial thromboembolectomy. In a retrospective study, 63 thromboembolectomies were analysed in 59 patients with acute ischaemia of the upper limbs (51 embolectomies and 12 thrombectomies). In 19 interventions, intraoperative angiography was performed either routinely or because of difficulty in passing the Fogarty catheter and/or absence of backflow. No angiography was performed in 44 interventions because the surgeons were dubious as to the benefits of the procedure. In 6/19 cases (32%) intraoperative angiography led to an extension of the intervention, with 1 intraoperative transluminal angioplasty, 2 patchplasties, 4 distal thromboembolectomies and 2 thromboendarterectomies. In patients with embolic occlusion, the adoption of routine intraoperative angiography resulted in a significantly lower re-occlusion rate at 6 months in comparison with patients who were not submitted to angiography (P<0.05). Also in patients with thrombotic occlusion, the adoption of angiography resulted in a lower re-occlusion rate at 6 months compared to patients not submitted to angiography (P<0.05). There were no amputations at 1 month. We recommend intraoperative arteriography as a routine procedure due to its positive influence on the outcome of thromboembolectomy for acute upper limb ischaemia.

Laparoscopic minor pancreatic resections (enucleations/atypical resections). A long-term appraisal of a supposed mini-invasive approach.

INTRODUCTION: A few retrospective, small, often multicentric studies show encouraging results of laparoscopic minor pancreatic surgery, but do not allow for an evaluation of feasibility and effectiveness. AIM: Evaluation of the results of laparoscopic minor pancreatic resections (LMPR), including atypical resections and enucleations. MATERIAL AND METHODS: The outcome of all consecutive patients undergoing LMPR in a tertiary care university hospital specializing in the laparoscopic approach to solid organs (I.M.M., Paris - France) was retrospectively evaluated by the analysis of operating time, blood loss, conversion, morbidity, stay and late outcome. RESULTS: Thirty-three patients underwent LMPR (29 enucleations and 4 atypical resections) for various diseases. The conversion rate was 21%, mean operating time 189 min, and mean blood loss 133 ml. Morbidity was 60%; 10 patients (30%) presented a pancreatic fistula. Pancreatic fistula was independent of type of resection, technique of pancreas section, management of enucleated surface and somatostatin administration. Median stay for enucleations was 18 days. Mean follow-up was 61 months. CONCLUSIONS: Laparoscopic pancreatic enucleation is feasible and safe, with no mortality, no lengthening of operating time and a high success rate. Conversely, it does not imply a reduction in complications or hospital stay at the present state of the art.

A critical appraisal of laparoscopic pancreatic enucleations: right-sided procedures (Pancreatic Head, Uncus) are not mini-invasive surgery.

Laparoscopic pancreatic enucleation is increasingly performed worldwide. Few small-sized series show encouraging results, especially after enucleations performed for lesions located in the left part of the pancreas. The outcome of laparoscopic pancreatic enucleations was retrospectively evaluated by the analysis of prospectively collected parameters. Results of right-sided (head/uncus) and left-sided (neck/body/tail) enucleations were compared. From 1997 to 2010, 25 patients underwent laparoscopic pancreatic enucleation. The conversion rate was 12%, mean operating time was 158 minutes, and mean blood loss was 106 mL. Morbidity was 56% and the rate of pancreatic fistula 32%. Outcome differed between patients undergoing right-sided and left-sided enucleations, the operative time being 178 versus 132 minutes, morbidity 64% versus 45%, and median hospital stay 26 versus 9 days, respectively. Pancreatic enucleation is feasible by laparoscopy, with a high success rate and no mortality but significant morbidity. Laparoscopy seems to be of no use in right-sided procedures. Pancreatic fistula is still the main cause of long-lasting morbidity.

Predictive factors of morbidity in distal pancreatic resections.

OBJECTIVE: To evaluate the postoperative morbidity of distal pancreatic resections and to investigate its predictive factors. METHODS: The study was conducted retrospectively from a prospectively database maintained. From 1994 to 2008, 100 consecutive patients underwent left pancreatic resections. The primary variable of interest was postoperative morbidity, and various other characteristics of the population were simultaneously recorded. Later, for the analysis of predictors of postoperative morbidity, the subgroup of patients who underwent distal pancreatectomy with spleen preservation (n = 65) was separately analyzed with regards to the different techniques of section of the pancreatic parenchyma, as well as to other possible predictors of postoperative morbidity. RESULTS: Considering all left pancreatic resections performed, the occurrence of overall, relevant and serious complications was 55%, 42% and 20%, respectively. The factors predictive of postoperative morbidity after distal pancreatectomy with spleen preservation were the technique employed for section of the pancreatic parenchyma, age, body mass index and the performance of concomitant abdominal operations. CONCLUSION: The morbidity associated with pancreatic resections to the left of the superior mesenteric vessels was high. According to the stratification adopted based on the severity of complications, some predictive factors have been identified. Future studies with larger cohorts of patients are needed to confirm these results.

Lessons learned from the first 100 laparoscopic liver resections: not delaying conversion may allow reduced blood loss and operative time.

BACKGROUND: The laparoscopic approach to liver resective surgery is slowly spreading to specialized centers. Little is known about factors influencing the immediate postoperative outcome. STUDY DESIGN: The purpose of the study was to evaluate the immediate outcome of laparoscopic liver resection (LLR), with particular emphasis on intraoperative bleeding and conversion. A retrospective analysis of demographic, clinical, and surgical data, including conversion, morbidity/mortality, and hospital stay, of the first 100 patients at our institution undergoing LLR from February 1997 through March 2007 was performed. RESULTS: Indication for LLR was benign lesion in 28 patients, malignancy in 33, and living donation in 39. Seventy-five resections involved two or more segments. Mean blood loss was 120 ± 127.6 mL. One patient (1%) required transfusion. Mean operative time was 253 ± 91.6 minutes. No patient died. Postoperative complications occurred in 21 patients. The conversion rate was 17%. Variables related to conversion were American Society of Anesthesiologists Class II, body mass index, cirrhosis, necessity for the Pringle maneuver, and intraoperative blood loss. Conversion did not influence the operative time. Patients with conversion had more complications and a longer hospital stay. CONCLUSIONS: Liver resection by laparoscopy is feasible and safe, implying low intraoperative blood loss. Not perfect physical conditions, cirrhosis, high body mass index, and, intraoperatively, blood loss and the necessity of a Pringle maneuver should be considered risk factors for conversion. A meticulous dissection by bipolar coagulation, Harmonic(®) (Ethicon) scalpel, and ultrasound dissector, other than the attitude not to delay conversion in difficult cases, may allow for low blood loss without prolongation of operative time, with a possible, slight increase of the conversion rate.

Pancreatic fistula after pancreaticoduodenectomy: the conservative treatment of choice.

BACKGROUND: A pancreatic fistula (PF) is the most common complication after pancreaticoduodenectomy (PD), and its reported incidence varies from 2% to 28%. The aim of the present study was to analyse the treatment of a complicated PF comparing the surgical approach with conservative techniques. METHODS: From January 2000 through to August 2006, 121 patients were submitted for PD. The study consisted of 70 men and 47 women, with a median age of 60 years (SD +/- 12). The main indications for PD were pancreatic duct carcinoma in 52 patients (44.5%), ampullary carcinoma or adenoma in 18 (15.4%) and islet cell tumour in 11 (9.4%). Reconstruction by pancreatogastrostomy was performed in 65 patients (55.6%), and pancreatojejunostomy in 52 patients (44%). RESULTS: Thirty-five patients (30%) developed a PF. Amongst these, 20 were managed conservatively and 14 were reoperated. These two groups of patients were compared with patients without a PF for analysis. There was no significant difference in the mean age, the gender ratio, American Society of Anesthesiologists (ASA) classification, surgical time and blood replacement, number of associated procedures, vascular resection and type of reconstruction between the three groups. There were five post-operative deaths (4.2%), three patients (21.4%) in the surgical treatment group (P < 0.01). Mean total number of complications (P= 0.02) and mean length of hospital stay (P < 0.001) were greater in the surgical group. The medium delay between the pancreatic resection and reoperation was 10 days (range, 3-32 days). Completion splenopancreatectomy was required in five patients whereas conservative treatment including debridement and drainage was applied in nine patients. CONCLUSION: The surgical approach for a PF is associated with a higher mortality and morbidity. There is no advantage in performing completion pancreatectomy (CP) instead of extensive drainage as a result of the same mortality and morbidity rates and the risk of endocrine insufficiency. In cases of complicated PF, radiological or surgical conservative treatment is recommended.

Treatment of stage IVA hepatocellular carcinoma: should we reappraise the role of surgery?

HYPOTHESIS: A subset of patients with stage IVA hepatocellular carcinoma (HCC) and preserved liver function may benefit from hepatic resection. DESIGN: Retrospective review of a prospectively collected database. SETTING: An academic tertiary care hepatobiliary unit. PATIENTS: Twenty patients who underwent surgical treatment for stage IVA HCC between July 1998 and October 2004 were identified from the database. INTERVENTION: Intraoperative ablation of HCC nodules was combined with resection in 6 patients (30%) to increase resectability. Three patients also underwent resection of extrahepatic tumors. Five patients (25%) had macroscopic invasion of the portal vein and 2 patients (10%) underwent thrombectomy of the vena cava. MAIN OUTCOME MEASURES: Intraoperative data, recurrence, and long-term survival rates were analyzed. RESULTS: Postoperative mortality and morbidity were 5% and 30%, respectively. The median number of resected tumors per patient was 3, and the median diameter of the largest tumor was 60 mm. With a median follow-up of 23 months, 14 patients (70%) developed recurrence. Treatment of recurrence was possible in 10 patients and included transarterial chemoembolization in 7 patients (35%), of whom 2 (10%) had radiofrequency ablation first, and systemic chemotherapy in 3 patients (15%). Median survival time was 32 months, and the actuarial 1-, 3-, and 5-year survival rates were 73%, 56%, and 45%, respectively. CONCLUSIONS: Long-term survival can be achieved using an aggressive surgical approach in select patients with advanced HCC. Patients with stage IVA HCC should be followed up by a multidisciplinary team because recurrence is common and sequential treatments may prolong survival.

TIMP-2 modulates neointimal formation in experimental ePTFE arterial grafts.

BACKGROUND: In vascular reconstructive surgery, myointimal hyperplasia contributes to the adverse outcome of synthetic grafts. This phenomenon is because of unregulated extracellular matrix degradation and remodeling, and excessive smooth muscle cell proliferation and migration. Matrix metallopreoteinase 2 (MMP-2) is known as an important contributor to these events. The aims of our study was to investigate the effects of selective MMP-2 inhibitor (TIMP-2) in endothelialization rate, SMC proliferation, and myointimal hyperplasia in experimental ePTFE arterial grafts. METHODS: In 20 male Lewis rats, a 1-cm long ePTFE graft has been inserted at the level of the abdominal aorta. Animals were randomized in two groups (10 animals each): group A received six subcutaneous inoculations of TIMP-2 (2.5 microg) after surgery, group B received only the vehicle of TIMP-2. RESULTS: Neointimal thickness, as well as SMC density, were augmented in group B, whereas endothelial cells density was augmented in group A, and these findings were statistically significant. In group A SMC were better organized, just like SMC of thoracic aorta. In group B SMC were no organized. Furthermore, anti-TIMP-2 and anti-MMP-2 coloration revealed higher levels of TIMP-2 and lower levels of MMP-2 in group A versus group-B. CONCLUSIONS: Use of TIMP-2 affects the neointimal formation of experimental e-PTFE arterial grafts, leading to a better-organized neointima, with improved endothelialization.

Fatores preditivos de morbidade nas ressecções pancreáticas esquerdas / Predictive factors of morbidity in distal pancreatic resections

OBJETIVO: Avaliar a morbidade pós-operatória e investigar a existência de seus fatores preditivos. MÉTODOS: O estudo foi realizado de forma retrospectiva, a partir de uma base de dados mantida de forma prospectiva. De 1994 a 2008, 100 pacientes consecutivos foram submetidos à ressecções pancreaticas esquerdas. A principal variável de interesse foi a morbidade pós-operatória, tendo diversas outras características da população sido registradas simultaneamente. Posteriormente, para a análise de fatores preditivos de morbidade pós-operatória o subgrupo de pacientes que foi submetido aos procedimentos de pancreatectomia distal com preservação do baço (n=65) foi analisado separadamente quanto à relevância das diferentes técnicas de secção do parênquima pancreático, assim como, outros possíveis fatores preditivos à ocorrência de morbidade pós-operatória. RESULTADOS: Considerando-se juntamente todas as ressecções pancreáticas esquerdas realizadas, a ocorrência de complicações globais, de complicações relevantes e graves foi 55%, 42% e 20%, respectivamente. Os fatores que se mostraram preditivos à ocorrência de morbidade pós-operatória após pancreatectomia distal com preservação do baço foram a técnica de secção do parênquima pancreático, idade, índice de massa corporal e a realização de operação abdominal concomitante. CONCLUSÃO: A morbidade associada às ressecções pancreáticas, à esquerda dos vasos mesentéricos superiores, foi importante. De acordo com a estratificação adotada baseada na gravidade das complicações, alguns fatores preditivos foram identificados. Estudos futuros com coortes maiores de pacientes são necessários para confirmar tais resultados.

OBJECTIVE: To evaluate the postoperative morbidity of distal pancreatic resections and to investigate its predictive factors. METHODS: The study was conducted retrospectively from a prospectively database maintained. From 1994 to 2008, 100 consecutive patients underwent left pancreatic resections. The primary variable of interest was postoperative morbidity, and various other characteristics of the population were simultaneously recorded. Later, for the analysis of predictors of postoperative morbidity, the subgroup of patients who underwent distal pancreatectomy with spleen preservation (n = 65) was separately analyzed with regards to the different techniques of section of the pancreatic parenchyma, as well as to other possible predictors of postoperative morbidity. RESULTS: Considering all left pancreatic resections performed, the occurrence of overall, relevant and serious complications was 55%, 42% and 20%, respectively. The factors predictive of postoperative morbidity after distal pancreatectomy with spleen preservation were the technique employed for section of the pancreatic parenchyma, age, body mass index and the performance of concomitant abdominal operations. CONCLUSION: The morbidity associated with pancreatic resections to the left of the superior mesenteric vessels was high. According to the stratification adopted based on the severity of complications, some predictive factors have been identified. Future studies with larger cohorts of patients are needed to confirm these results.

Vascular endothelial growth factor increases the migration and proliferation of smooth muscle cells through the mediation of growth factors released by endothelial cells.

BACKGROUND: Vascular endothelial growth factor (VEGF), a highly specific chemotactic and mitogenic factor for vascular endothelial cells (EC), appears to be involved in the development of atherosclerosis. The purpose of our study was to assess if VEGF might indirectly stimulate SMC migration and proliferation in a EC-SMC coculture system, through the mediation of growth factors released by EC. METHODS: Bovine aortic SMC were cocultured with bovine aortic EC treated with hrVEGF, to assess SMC proliferation and migration. The release and mRNA expression of basic fibroblast growth factor (bFGF) and transforming growth factor beta(1) (TGFbeta(1)) were assessed by ELISA and PCR analysis. RESULTS: hrVEGF (10 ng/ml), added to EC cocultured with SMC, induced a significant increase in tritiated thymidine uptake by SMC as compared to controls (P < 0.01) and a significant increase in SMC migration in respect to control (27%; P < 0.01). EC stimulated with hrVEGF increased the release and the expression of bFGF and decreased the release and the expression of TGFbeta(1) with a statistically significant difference in respect to controls (P < 0.001). CONCLUSIONS: VEGF indirectly stimulates SMC proliferation and migration through the modulation of bFGF and TGFbeta(1) released by EC.