Severe acute pancreatitis: eight fundamental steps revised according to the 'PANCREAS' acronym.

Severe acute pancreatitis remains a life-threatening condition, responsible for many disorders of homeostasis and organ dysfunction. By means of a mnemonic 'PANCREAS', eight important steps in the management of severe acute pancreatitis are highlighted. These steps follow the principle of goal-directed therapy and should be borne in mind after diagnosis and during clinical treatment. The first step is perfusion: the goal is to reach a central venous pressure of 12-15mmHg, urinary output 0.5-1ml/kg/hour and inferior vena cava collapse index greater than 48%. Next is analgesia: multimodal, systemic and combined pharmacological agent and epidural block are possibilities. Third is nutrition: precocity, enteral feeding in gastric or post-pyloric position. Parenteral nutrition works best in difficult cases to achieve the individual total caloric value. Fourth is clinical: mild, moderate or severe pancreatitis according to the Atlanta criteria. Radiology is fifth: abdominal computed tomography on the fourth day for prognosis or to modify management. Endoscopy is sixth: endoscopic retrograde cholangiopancreatography (cholangitis, unpredicted clinical course and ascending jaundice); management of pancreatic fluid collection and 'walled-off necrosis'. Antibiotics come next: infectious complications are common causes of morbidity. The only rational indication for antibiotics is documented pancreatic infection. The last step is surgery: the dogma is represented by the 'three Ds' (delay, drain, debride). The preferred method is a minimally invasive step-up approach, which allows for gradually more invasive procedures when the previous treatment fails.

Two's a Charm: Endoscopic Therapy of Multiple Pancreatic Pseudocysts.

Pancreatic pseudocysts commonly complicate acute pancreatitis. They can evolve either asymptomatically or with important symptoms. Treatment can be surgical, endoscopic, or percutaneous. The authors present a case report of a 78-year-old man who developed symptoms of an acute abdomen during hospitalization. A CT scan showed two pancreatic pseudocysts (diameters 10 cm and 7.5 cm) that were successfully drained endoscopically. Multiple pancreatic pseudocysts can be treated successfully via an endoscopic approach.

Endoscopic submucosal dissection for superficial premalignant and malignant epithelial neoplasms of the digestive tract: a real-life experience in Italy.

OBJECTIVE: Endoscopic submucosal dissection (ESD) is a technique for en bloc resection of neoplastic lesions of the digestive tract. Endoscopic submucosal dissection was developed in Asia, and data from Western countries are scarce. Our study aimed to assess the efficacy and safety of ESD for resection of superficial premalignant and malignant epithelial neoplasms in a tertiary center in Italy. PATIENTS AND METHODS: All patients with gastrointestinal lesions who underwent ESD between January 2013 and December 2018 in our center were retrospectively evaluated. Technical success, en bloc, R0, curative resection, and complication rates were assessed. RESULTS: A total of 107 lesions (stomach, no.=41; rectum, no.=32; colon, no.=28; esophagus, no.=5; duodenum, no.=1) were resected by ESD in 93 patients. Endoscopic submucosal dissection was technically successful in 99.1% (106/107) of lesions. Among the 90 superficial premalignant and malignant epithelial neoplasms, en bloc, and R0 resection rates were 97.8% (no.=88) and 75.6% (no.=68), respectively. Major complications occurred in 9.3% (10/107) of cases: 4 (3.7%) were perforations and 6 (5.6%) were major bleedings. All complications, but two which needed surgery, were managed endoscopically. CONCLUSIONS: Our study shows that ESD is a feasible, effective, and safe technique in a Western country.

The Great View Forward: The Use of a Colonoscope for Distal Duodenal Stent Placement.

INTRODUCTION: Stent placement in the distal duodenum can be difficult. We describe a case report of a 94-year-old man with metastatic pancreatic head cancer compressing the third and fourth portions of the duodenum, treated by endoscopic stent placement using a colonoscope. AREAS COVERED: A literature review highlighted two possible procedures for stent placement in the distal duodenum, namely forward-viewing and side-viewing endoscopies. Gastroscopes, duodenoscopes, enteroscopes, and colonoscopes have all been suggested for the purpose. For distal lesions, especially when the duodenal wall is stiffened due to compression or infiltration by neoplastic lesions, a conventional upper endoscope can be too short to reach the narrowed site in "push mode," necessitating the use of a longer endoscope. EXPERT COMMENTARY: A colonoscope can be safely and effectively used to accomplish distal duodenal stent placement.

"Cystamatic" Review: Is Surgery Mandatory for Pneumatosis Cystoides Intestinalis?

INTRODUCTION: Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by the presence of intramural gas cysts within the small and large intestines. We describe a case of a 70-year-old man admitted to the Emergency Surgery Department for PCI who was treated conservatively. AREAS COVERED: We reviewed 60 cases of PCI described in the international literature over the last 5 years. From our analysis, it appears that the etiology of the gas production within the submucosa or the subserosa of the gastrointestinal tract is still unknown. The rupture of the cysts can lead to pneumoperitoneum that can simulate a surgical emergency. EXPERT COMMENTARY: For patients with PCI, a conservative approach is the treatment of choice, with surgery mandatory only for complicated disease.

Subcapsular Hepatic Hematoma Post-ERCP: Case Report and Review of the Literature.

INTRODUCTION: Hepatic hematoma is a rare but possible complication of ERCP. We describe the case of a 75-year old man with a large, 8 × 12 cm, sub-capsular and intra-parenchymal hematoma post ERCP, affecting the right liver segments and treated conservatively. AREAS COVERED: A review of literature has been performed, highlighting two possible mechanisms: hematoma may occur as the result of accidental laceration of a small intrahepatic vessel by the guidewire, whereas the other hypothesis posits that the hepatic damage is secondary to traction on the biliary system exerted by the balloon. We speculate that in case of anomalies of the biliary tree, the incidence of this complication is higher than expected. EXPERT COMMENTARY: In case of hepatic hematoma post ERCP, a conservative approach should always be considered before proceeding to interventional radiologic procedures or to surgical therapy.

Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation.

Ferroptosis is a form of regulated non-apoptotic cell death that has been implicated in several disease contexts. A better understanding of the ferroptotic death mechanism could lead to the development of new therapeutics for degenerative diseases, and a better understanding of how to induce ferroptosis in specific tumor contexts. We performed an unbiased genome-wide siRNA screen to find genetic suppressors of ferroptosis. We determined that loss of CARS, the cysteinyl-tRNA synthetase, suppresses ferroptosis induced by erastin, which inhibits the cystine-glutamate antiporter known as system xc(-). Knockdown of CARS inhibited erastin-induced death by preventing the induction of lipid reactive oxygen species, without altering iron homeostasis. Knockdown of CARS led to the accumulation of cystathionine, a metabolite on the transsulfuration pathway, and upregulated genes associated with serine biosynthesis and transsulfuration. In addition, inhibition of the transsulfuration pathway resensitized cells to erastin, even after CARS knockdown. These studies demonstrate a new mechanism of resistance to ferroptosis and may lead to strategies for inducing and suppressing ferroptosis in diverse contexts.

A retrospective analysis of early and late outcome of biodegradable stent placement in the management of refractory anastomotic colorectal strictures.

BACKGROUND: Benign colorectal strictures are treated conventionally by endoscopic dilation. Experience using SEMS for benign colonic strictures is limited, and outcomes to date have been disappointing. Refractory colorectal strictures remain challenging to be treated with surgery. Polydioxanone-based stent are biodegradable (BD) stent CE approved for esophageal strictures. This study was designed to investigate retrospectively the safety and the efficacy of these stents for the management of strictures refractory to multiple sessions of dilation. METHODS: Patients with postsurgical benign strictures located within 20 cm from anal verge, refractory to mechanical or pneumatic dilation (at least 3 sessions) were included in this analysis. Clinical success was defined as the absence of occlusive symptoms and the ability to pass through the stricture with a regular size colonoscope. All patients were predilated before stent placement. Stents were released under fluoroscopic control. All patients were under stool softeners for 3 months. Follow-up was scheduled with endoscopic and fluoroscopic controls within 90 days from stent deployment and afterwards by telephone interview and/or ambulatory consultation. RESULTS: Eleven patients (7 males, mean age 62.3 ± 8.5 years) were included. Technical success was achieved in all the patients. Stent migration was observed in four patients within the first 2 weeks after stent placement. Stent migration was followed by recurrence of stricture and obstructive symptoms in all the cases. Among the seven patients who completed the process of stent biodegradation, five of them had complete resolution of the stricture and relief of symptoms. Two of 11 patients required surgical treatment during the follow-up period (mean 19.8 (range 42-15) months). The overall success rate of the BD stent was 45 %. CONCLUSIONS: This retrospective analysis of a limited number of patients demonstrated that nondedicated esophageal BD stents are associated with high risk of migration and clinical success in less than 50 % of patients. Dedicated stents with large diameter and antimigration findings could potentially improve the outcome of patients with refractory benign colorectal strictures.

Efficacy and safety of endoscopic submucosal dissection for colorectal neoplasia: a systematic review.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) has been proposed for large colorectal lesions, due to the high risk of recurrence following endoscopic mucosal resection. However, data on the efficacy and safety of colorectal ESD are still controversial. The aim of the current systematic review was to assess the efficacy and safety of colorectal ESD. METHODS: A detailed Medline search of papers published during the period 1999-2010 was performed, using the search terms "Endoscopic submucosal dissection," "Colorectal neoplasia," "Colon," or "Rectum." Published studies that evaluated ESD for colorectal lesions were assessed using well-defined inclusion/exclusion criteria, including histological confirmation and surgery for complications. The process was independently performed by two authors. Forest plots on primary (i.e. histologically verified R0 resection and surgery for ESD complications) and secondary end-points were produced based on random-effect models. Heterogeneity was assessed using the I2 statistic. Risk for within-study bias was also ascertained. RESULTS: A total of 22 studies (20 Asian, two European) provided data on 2841 ESD-treated lesions. The per-lesion summary estimate of R0 resection rate was 88% (95%CI 82%-92%; I2=91%). At meta-regression, carcinoid vs. non-carcinoid series (R0 93% vs. 87%; P=0.04) and Asian vs. European series (R0 88% vs. 65%; P=0.03) appeared to explain the detected heterogeneity. The per-lesion summary estimate of surgery for ESD complications was 1% (95%CI 0%-1%) with a moderate degree of heterogeneity (I2=49%). However, subgrouping of these results according to histological tumor types was not available in the reviewed studies. CONCLUSIONS: ESD appeared to be an extremely effective technique to achieve R0 resection of large colorectal lesions. The very low rate of surgery for complications also shows the potential safety of this approach.

Safety of cold polypectomy for <10mm polyps at colonoscopy: a prospective multicenter study.

BACKGROUND: Cold polypectomy techniques (without electrocautery) by means of biopsy forceps or snare are widely adopted for the removal of subcentimetric polyps. However, few data are available on the safety of this approach. The aim of this study was to assess the safety of cold polypectomy for subcentimetric polyps, as well as the rate of advanced neoplasia in these lesions. PATIENTS AND METHODS: In a prospective multicenter trial, consecutive patients with at least one < 10-mm polyp at colonoscopy were prospectively included. All of the < 10-mm polyps detected within the study period were removed by cold polypectomy. The rates of immediate or delayed bleeding and other complications were assessed at 7 and 30 days after cold polypectomy by telephone calls. The rate of advanced histology was also assessed. Predictive variables of postpolypectomy bleeding or advanced neoplasia were identified by multivariate analysis. RESULTS: A total of 1015 < 10-mm polyps in 823 patients (15.5 % on antiplatelet agents) were removed. Of these, 822 (81 %) were ≤ 5 mm and 193 (19 %) were 6 - 9 mm. Immediate postpolypectomy bleeding occurred in 18 patients, corresponding to a per-patient and per-polyp bleeding rate of 2.2 % (95 % confidence interval [CI] 1.2 % - 3.2 %) and 1.8 % (95 %CI 1 % - 2.6 %), respectively. Therapy with antiplatelet agents (odds ratio [OR] 4; 95 %CI 1.5 - 10.6) and larger polyp size (OR 2; 95 %CI 1.1 - 6.9) were independent predictors of bleeding. Bleeding was successfully treated by endoscopic hemostasis in all cases and required no further medical intervention. Advanced neoplasia prevalence in polyps ≤ 5 mm was as high as 8.7 %. CONCLUSIONS: The results from this study showed the high safety of a cold polypectomy approach for subcentimetric polyps. This was due to the low rate of postpolypectomy bleeding and to the high efficacy of endoscopic hemostasis in its treatment. The high rate of advanced neoplasia in polyps ≤ 5 mm should prompt some caution on the management of these lesions following detection at computed tomography colonography or colon capsule endoscopy.

Balanced Propofol Sedation in Patients Undergoing EUS-FNA: A Pilot Study to Assess Feasibility and Safety.

Introduction and aims. Balanced propofol sedation (BPS) administered by gastroenterologists has gained popularity in endoscopic procedures. Few studies exist about the safety of this approach during endosonography with fine needle aspiration (EUS-FNA). We assessed the safety of BPS in EUS-FNA. Materials and methods. 112 consecutive patients, referred to our unit to perform EUS-FNA, from February 2008 to December 2009, were sedated with BPS. A second gastroenterologist administered the drugs and monitorized the patient. Results. All the 112 patients (62 males, mean age 58.35) completed the examination. The mean dose of midazolam and propofol was, respectively, of 2.1 mg (range 1-4 mg) and 350 mg (range 180-400). All patients received oxygen with a mean flux of 4 liter/minute (range 2-6 liters/minute). The mean recovery time after procedure was 25 minutes (range 18-45 minutes). No major complications related to sedation were registered during all procedures. The oxygen saturation of all patients never reduced to less than 85%. Blood systolic pressure during and after the procedure never reduced to less than 100 mmHg. Conclusions. In our experience BPS administered by non-anaesthesiologists provided safe and successful sedation in patients undergoing EUS-FNA.

Transoral treatment of Zenker diverticulum: flexible endoscopy versus endoscopic stapling. A retrospective comparison of outcomes.

Transoral stapled diverticulo-esophagostomy (TSDE) has gained increased popularity in surgical treatment of Zenker diverticulum (ZD). One of the advantages of this approach is early rehabilitation with significant decrease in patient morbidity and time to resumption of oral intake as compared with open treatment. The section of the septum between the diverticulum and the esophagus with a flexible endoscopic (ES) approach has also been proposed since mid-90s as an alternative for treatment of ZD. Both these approaches are a minimally invasive approach to treat ZD. We compared the TSDE management of ZD versus the ES treatment in a retrospective consecutive series of patients who were referred to either the ES or surgical unit of our Institute. Fifty-eight consecutive patients underwent treatment for ZD either by TSDE or ES. The two techniques were evaluated for length of hospital stay, diverticulum size, resumption of oral intake, resolution of dysphagia, and complications. Clinical outcome was evaluated throughout a symptom score from 0 to 3, calculated before and after the procedure. The two groups were compared on the various parameters using a Mann--Whitney test. Twenty-eight patients underwent ES and 30 TSDE for ZD. In both groups, a significant decrease in postoperative versus preoperative dysphagia was reported. The average length of hospital stay wasn't significantly different in the two groups (3.38 days for TSDE vs. 2.42 days for ES). The overall complication rate was similar in the two groups. There were two cases in the ES group and three cases in the TDSE group that required an ES revision to take down a residual diverticular wall that produced a mild but persistent dysphagia. Minimally invasive treatment of ZD both with ES and with TSDE is a valuable option for this disease: both techniques are safe and effective, with similar outcome in terms of hospital stay, symptom reduction, and complication rate. Long-term results have to be evaluated.

Endoscopic flexible treatment of Zenker's diverticulum: a modification of the needle-knife technique.

BACKGROUND AND STUDY AIM: Endoscopic treatment of Zenker's diverticulum has been successfully reported over the last 10 years using different approaches. The hook-knife is a new device originally developed for endoscopic submucosal dissection procedures. This study aimed to investigate the safety and efficacy of endoscopic myotomy performed with the hook-knife. PATIENTS AND METHOD: From July 2005, 32 consecutive patients (23-male, mean age 74.8 years) with dysphagia secondary to the presence of Zenker's diverticulum were prospectively enrolled. Myotomy was performed using a straight-end transparent hood to the tip of the scope and the hook-knife for the incision of the bridge between the Zenker's diverticulum and the esophagus. Clinical outcome was evaluated assigning a dysphagia symptom score from 0 (symptoms absent) to 4 (inability to swallow saliva). RESULTS: General anesthesia was used in 4 patients, deep sedation with propofol in 23 patients, while midazolam was used in 5 patients. The mean procedural time was 28 minutes. Complications occurred in 2 patients (6.25 %). At 1 month follow-up, the mean dysphagia score was significantly improved from 2.9 to 0.6 ( P < 0.001) with 87.5 % of patients free of symptoms and 4 patients with dysphagia that was persistent but milder than before the treatment. Three of these 4 patients underwent a successful second endoscopic treatment with complete relief of dysphagia; one was not re-treated because of advanced age (92 years). During the follow-up period (23.87 +/- 9.6 months), 2 patients developed dysphagia recurrence. The overall success rate was 90.6 %. CONCLUSIONS: Diverticulectomy with a flexible scope and the hook-knife may represent a safe and effective alternative treatment for patients with Zenker's diverticulum.

Hydroxy-propyl-methyl-cellulose is a safe and effective lifting agent for endoscopic mucosal resection of large colorectal polyps.

BACKGROUND: Endoscopic mucosal resection (EMR) is today the treatment of choice for flat and sessile colorectal lesion, the only concern being completeness of resection. One of the major issues is the choice of the infiltrating substance to enable a long-lasting cushion under the lesion. The aim of this study was to prospectively evaluate safety and efficacy of hydroxy-propyl-methyl-cellulose (HPMC) injection for this purpose. PATIENTS: All flat and sessile lesions of the colon and rectum larger than 20 mm and considered suitable for EMR were included. In all cases 0.8% HPMC solution was injected through a 23G needle, in quantity according to the endoscopist's indication. Primary endpoints of the study were: (1) ability to perform en bloc resection of the lesions by using this new injection means, (2) complete resection rate, and (3) early and late complication rate. RESULTS: We resected 27 flat, sessile, or laterally spreading lesions up to 60 mm (28 mm average). Mean dose of HPMC injected was 10.2 ml (range 8-40 ml). Median procedure time was 32 min (range 15-105 min). En bloc resection was achieved in up to 21 cases (78%). Histologically detected complete tumour removal was achieved in 23 lesions, whereas lateral margins could not be properly evaluated in 4 cases due to coagulation artefacts. No perforation was observed. Procedural spurting bleeding was managed by epinephrine injection in one case and clip application in the remaining. Two case of local recurrence of adenomatous tissue were observed at 3 and 12 months, and treated by EMR. No complication related to the use of HPMC was observed. CONCLUSIONS: Injection of HPMC for EMR resulted safe and effective, allowing en bloc resection in the majority of cases with a limited number of complications. Continued progress in the field will include more outcomes research and techniques simplification.

Endoclipping for gastric perforation secondary to second session of EMRC in locally residual early gastric cancer: a case report.

A 72-year-old woman underwent gastric endoscopic mucosal resection with a cap-fitted endoscope for an adenocarcinoma in situ. She was scheduled for endoscopic follow-up at 1 and 3 months after the procedure. By the third month of follow up, biopsies of a slightly depressed scar area showed an high grade epithelial dysplasia. For this reason a second endoscopic resection (ER) was performed using the oblique soft cap. A perforation in the site of endoscopic resection was immediately observed. The complication was treated successfully by the application of seven clips.

Clinical experience with a new endoscopic over-the-scope clip system for use in the GI tract.

BACKGROUND: The newly designed over-the-scope clip (OTSC) seems to overcome several limitations of current clipping system, such as size and opening-closing force, allowing better control of gastric or colonic bleeding and/or deep wall defect or perforation. AIMS: The aim of this retrospective analysis was to describe the new endoscopic device and evaluate our first clinical experience. PATIENTS AND METHODS: We treated with the OTSC system 9 patients (range, 58-85 years; 6 men, 3 women) with bleeding and/or deep wall lesions of the GI tract. The OTSC system is composed of an application cap, which is mounted onto the distal tip of the endoscope and a connected releasing mechanism, installed on the handle of the scope. The rotation of the handle allows the release of the clip by a two tube sliding mechanism. RESULTS: All applications resulted successful, i.e. haemostasis was achieved, and/or wall defects could be closed. No complication was observed that could be ascribed to the clip itself or to the technique. CONCLUSIONS: The OTSC system is a new endoscopic tool for compression of large tissue areas and its indications are nonvaricose bleedings difficult to control and lesions or perforations of the GI tract. The initial clinical use of this clipping device proved to be efficient and effective.

Colifagina, a novel preparation of 8 lysed bacteria ameliorates experimental colitis.

Immune reactivity towards the bacterial intestinal flora plays an important part in the pathogenesis of inflammatory bowel disease. Administration of probiotic bacteria has beneficial effects on infectious and inflammatory diseases, principally in bowel disorders. However, little is known about the administration of soluble bacterial antigens in intestinal inflammation. We investigated the therapeutic effects of colifagina in experimental colitis. To assess this effect, C57BL/6 mice with dextran sulphate sodium-induced colitis were treated with colifagina, or with a placebo, for a period of 10 days. The mice were monitored, and inflammation was assessed by disease activity index (DAI). Analysis of fecal IgA concentration and measurement of IgA and inflammatory chemokine production in organ colonic culture was performed by ELISA. Clinically and histologically, bacterial-lysate-treated mice revealed significantly fewer DAI and a reduction of colonic histological inflammation. Treatment of healthy mice with colifagina significantly increased the fecal concentration of IgA and IgA production in organ culture. Colifagina administration in DSS-treated mice significantly increased the fecal concentration of IgA and IgA production in organ culture. MIP-1, MIP-2 and RANTES concentrations in colonic organ culture were significantly lower in colifagina-treated mice than in the placebo group. The use of colifagina is effective in amelioration of murine colitis.

Prognostic factors of survival in complicated viral and alcoholic cirrhosis without hepatocellular carcinoma. A retrospective study.

AIM: In several studies, attention is needed to one specific complication, in particularly to hepatocellular carcinoma, which modifies the natural history of liver cirrhosis. Thus, we performed a retrospective cohort analysis to clarify which complications, alone or in combination, are predictive factors of mortality in patients with viral or alcoholic cirrhosis without hepatocellular carcinoma. METHODS: Case records of 255 patients with decompensated viral or alcoholic cirrhosis between January 1990 and December 2000 were retrospectively analyzed. Relevant clinical and laboratory parameters, and their relationship to mortality, were studied. RESULTS: The mean duration of follow-up period was 29 months in which 178 patients (69.8%) died and 77 (31.8%) survived. None of the patients underwent liver transplantation. The cumulative mortality rate of patients with complicated cirrhosis was 38.8% after 1 year, 51.7% after 2 years, 61.1% after 3 years and 65.1% after 8 years. A multivariate Cox's model identified the following variables as significant: age (P=0.001), gastrointestinal bleeding (GB)-ascites combination (P=0.000), encephalopathy-GB-ascites (P=0.028), hepatorenal syndrome (HRS) (P=0.000), GB-spontaneous bacterial peritonitis (SBP) (P=0.001), alkaline phosphatase (ALP) (P=0.004) and the Child-Pugh score (P=0.000). CONCLUSION: The mortality in a group of patients with alcoholic cirrhosis is longer than in those with viral cirrhosis . Moreover, ascites in combination with other complications, HRS and hemorrage-SBP association are independent predictors of mortality in patients with complicated liver cirrhosis.