Comprehensive review on the pathogenesis of hypertriglyceridaemia-associated acute pancreatitis.

It is well known, that the inflammatory process that characterizes acute pancreatitis (AP) can lead to both pancreatic damage and systemic inflammatory response syndrome (SIRS). During the last 20 years, there has been a growing incidence of episodes of acute pancreatitis associated with hypertriglyceridaemia (HTAP). This review provides an overview of triglyceride metabolism and the potential mechanisms that may contribute to developing or exacerbating HTAP. The article comprehensively discusses the various pathological roles of free fatty acid, inflammatory response mechanisms, the involvement of microcirculation, serum calcium overload, oxidative stress and the endoplasmic reticulum, genetic polymorphism, and gut microbiota, which are known to trigger or escalate this condition. Future perspectives on HTAP appear promising, with ongoing research focused on developing more specific and effective treatment strategies.

Transanal total mesorectal excision (TaTME) in rectal cancer treatment within an expert center.

The objective of this study was to evaluate treatment outcomes in patients who underwent the TaTME procedure for cancer of the middle and low rectum in an expert center. Prospective analysis of the outcomes of all consecutive patients treated using the TaTME technique for cancer of the middle and distal rectum at the our medical center between March 1, 2015, and March 31, 2022. A total of 128 patients (34 women, 94 men; mean age 66.01 [38-85] years) with cancer of the middle and distal rectum qualified for TaTME. TaTME procedures were performed in 127/128 (99.22%) patients. Complications of surgery were observed in 22/127 (17.32%) patients. Negative proximal and distal margins were confirmed in all 127 patients. Complete (R0) resection of the mesorectum was confirmed in 125/127 (98.43%) and nearly complete (R1) resection was confirmed in 2/127 (1.57%) patients. The average follow-up period was 795 days (296-1522) days. Local recurrence was detected during the follow-up period in 2/127 (1.57%) patients. This study showed that the TaTME procedure is an effective and safe method for the minimally invasive treatment of middle and low rectal cancers, particularly within an expert center setting.

Efficacy, safety, and predictors of fruquintinib plus anti-programmed death receptor-1 (PD-1) antibody in refractory microsatellite stable metastatic colorectal cancer in a real-world setting: a retrospective cohort study.

Background: Patients with microsatellite stable (MSS) advanced colorectal cancer (CRC) have few alternatives for salvage therapy and a large unmet clinical need. Preclinical studies demonstrate that fruquintinib combined with anti-programmed death protein 1 (PD-1) has a synergistic anti-tumor effect. But a few phase 2 clinical studies show inconsistent efficacy of this combination therapy in CRC. The aim of this study was to investigate the efficacy, safety, and predictors of fruquintinib plus PD-1 antibodies in refractory MSS metastatic CRC (mCRC) in a real-world setting. Methods: We performed a retrospective single-center analysis to assess the outcomes of patients with MSS mCRC who were treated with fruquintinib plus anti-PD-1 antibodies subsequent to the failure of standard therapies at the Hunan Cancer Hospital. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were reviewed and evaluated. The primary endpoint was OS. The impact on OS and PFS was examined using the Cox regression model. Results: Between 1 January 2019 and 30 June 2022, we enrolled 70 eligible patients. The median follow-up was 17.2 months (range, 5.3-32.9 months). The median OS (mOS) and median PFS (mPFS) were 19.48 and 5.5 months respectively. The ORR was 11.43% and the DCR was 84.29%. Multivariate Cox regression analysis reveals liver metastasis (LM) without local treatment was a risk factor for OS [hazard ratio (HR) =5.31, P=0.0184], whereas that with local treatment (HR =2.19, P=0.263) was not. The most common adverse events were hand-foot syndrome (37.14%), hypertension (34.29%), mucositis oral (32.86%). No serious adverse effects or adverse effect-related deaths were reported. There were no instances of severe adverse effects or deaths related to adverse effects reported. Conclusions: Our study indicates that the combination of fruquintinib and anti-PD-1 antibodies can improve the OS and PFS with a tolerable toxicity profile for Chinese patients with refractory MSS mCRC. LM without local therapy is a negative prognostic factor for OS, but those with local treatment can significantly prolong survival. We require additional well-structured, prospective, and extensive studies to confirm and validate these findings.

Endoscopic treatment of pancreaticopleural fistulas.

Introduction: Pancreaticopleural fistula (PPF) is a serious complication of acute and chronic pancreatitis. Objective: To evaluate the effectiveness of various endoscopic techniques for the treatment of patients with PPFs. Methodology: Prospective analysis of the results of endoscopic treatment of 22 patients with PPF due to pancreatitis was conducted at the Department of General, Gastroenterological, and Oncological Surgery, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, between 2018 and 2021. Results: PPF was diagnosed in 22 patients (21 men and 1 woman; mean age 49.52 [30-67] years) with pancreatitis. In 19/22 (86.36%) patients, PPF communicated with the left pleural cavity and in 3/22 (13.64%) patients with the right pleural cavity. Chronic pancreatitis was diagnosed in 14/22 (63.64%) patients. Symptomatic pancreatic fluid collections were found in 15/22 (68.18%) patients with PPF (pancreatic pseudocyst in 11 and walled-off pancreatic necrosis in four patients). Endoscopic retrograde cholangiopancreatography was performed in 21/22 (95.45%) patients, confirming the diagnosis of PPF. All 21 patients underwent endoscopic sphincterotomy with prosthesis implantation in the main pancreatic duct (passive transpapillary drainage). In 1/22 (4.55%) patients, active transmural/transgastric drainage of the PPF was necessary due to inflammatory infiltration of the peripapillary region, precluding endoscopic pancreatography. Endoscopic transmural drainage was performed in all the 15 patients with pancreatic fluid collection. Clinical success was achieved in 21/22 (95.45%) patients. The mean total time of endotherapy was 191 (range 88-712) days. Long-term success of endoscopic treatment of PPFs during one year follow-up period was achieved in 19/22 (86.36%) patients. Conclusions: Endoscopic treatment is effective for managing post-inflammatory PPFs. The preferred treatment method is passive transpapillary drainage (prosthesis of the main pancreatic duct). If transpapillary drainage is not feasible, transmural drainage of the PPF remains the preferred method. Endoscopic transmural drainage leads to closure of the fistula canal in patients with pancreatic fluid collection complicated by PPF.

The Role of Antibiotics in Endoscopic Transmural Drainage of Post-Inflammatory Pancreatic and Peripancreatic Fluid Collections.

Background: Although endoscopic treatment of symptomatic post-inflammatory pancreatic and peripancreatic fluid collections (PPPFCs) is an established treatment method, some aspects of endotherapy and periprocedural management remain controversial. The role of antibiotics is one of the most controversial issues in interventional endoscopic management of local complications of pancreatitis. Methods: This study was a randomized, non-inferiority, placebo-controlled, and double-blinded clinical trial to investigate the role of antibiotic prophylaxis in endoscopic transmural drainage in patients with symptomatic non-infected PPPFCs and assess the influence of antibiotic treatment on the results of endotherapy in patients with symptomatic infected PPPFCs.This trial included 62 patients treated endoscopically for PPPFCs in 2020 at our medical center. Patients were divided into two groups; group 1 comprised patients who had received empirical intravenous antibiotic therapy during endotherapy and group 2 comprised patients who did not receive antibiotic therapy during endoscopic drainage of PPPFCs. The end points were clinical success and long-term success of endoscopic treatment. Results: Thirty-one patients were included in group 1 (walled-off pancreatic necrosis [WOPN, 51.6%; pseudocyst, 48.4%) and 31 patients in group 2 (WOPN, 58.1%; pseudocyst, 41.9%) (p=0.6098/nonsignificant statistical [NS]). Infection with PPPFCs was observed in 15/31 (48.39%) patients in group 1 and in 15/31 (48.39%) patients in group 2 (p=1.0/NS). The average time of active (with flushing through nasocystic drainage) drainage in group 1 was 13.0 (6 - 21) days and was 14.0 (7 - 25) days in group 2 (p=0.405/NS). The average total number endoscopic procedures on one patient was 3.3 (2 - 5) in group 1 and 3.4 (2 - 7) in group 2 (p=0.899/NS). Clinical success of PPPFCs was observed in 29/31 (93.5%) patients from group 1 and in 30/31 (96.8%) patients from group 2 (p=0.5540/NS). Complications of endotherapy were noted in 8/31 (25.8%) patients in group 1 and in 10/31 (32.3%) patients in group 2 (p=0.576/NS). Long-term success in group 1 and 2 was reported in 26/31 (83.9%) and 24/31 (77.4%) patients, respectively (p=0.520/NS). Conclusions: The effective endoscopic drainage of sterile PPPFCs requires no preventive or prophylactic use of antibiotics. In infected PPPFCs, antibiotic therapy is not required for effective endoscopic transmural drainage.

Percutaneous Endoscopic Necrosectomy-A Review of the Literature.

In this article, an attempt was made to clarify the role of percutaneous endoscopic necrosectomy (PEN) in the interventional treatment of pancreatic necrosis. A comprehensive review of the current literature was performed to identify publications on the role of PEN in patients with consequences of acute necrotizng pancreatitis. The aim of the study was to review the literature on minimal invasive necrosectomy, with emphasis on PEN using esophageal self-expanding metal stents (SEMS). The described results come from 15 studies after a review of the current literature. The study group comprised 52 patients (36 men and 16 women; mean age, 50.87 (13-75) years) with walled-off pancreatic necrosis, in whom PEN using a self-expandable esophageal stent had been performed. PEN was successfully completed in all 52 patients (100%). PEN complications were observed in 18/52 (34.62%) patients. Clinical success was achieved in 42/52 (80.77%) patients, with follow-up continuing for an average of 136 (14-557) days. In conclusion, the PEN technique is potentially effective, with an acceptable rate of complications and may be implemented with good clinical results in patients with pancreatic necrosis.

The Role of Endoscopic Ultrasound-guided Transmural Approach in the Management of Biliary Obstructions.

BACKGROUND: Transpapillary biliary drainage in endoscopic retrograde cholangiopancreatography (ERCP) is an established method for treatment of patients with benign and malignant biliary obstruction. However, attempts to gain access to the biliary tract through the major duodenal papilla during ERCP have been unsuccessful in some patients. This study aims to determine the role of endoscopic ultrasonography (EUS)-guided transmural approach in biliary endotherapy in case of failed ERCP. MATERIALS AND METHODS: A prospective analysis of the treatment outcomes of all 896 patients with obstructive jaundice secondary to biliary obstruction, who underwent endoscopic treatment in the years 2016-2021 at our institution. RESULTS: Effective drainage of bile ducts through the major duodenal papilla during ERCP was achieved in 772/896 (86.16%) patients with biliary obstruction. In 124/896 (13.84%) patients [92 males, 32 females; mean age 63.52 (46 to 89) y] ERCP failed and EUS-guided transmural approach was performed. Benign biliary obstruction was identified in 17/124 (13.71%) patients; the remaining 107/124 (86.29%) were diagnosed with malignant biliary obstruction. EUS-guided endoscopic transpapillary biliary tract stenting with transmural access was performed in 21/124 (16.94%) patients; the remaining 103/124 (83.06%) required extra-anatomic transmural anastomosis of the bile ducts to the gastrointestinal tract. Technical success was achieved in 121/124 (97.58%) patients, while clinical success was achieved in 112/124 (90.32%). Complications were reported in 15/124 (12.1%) patients; with early complications in 12 and late complications in 3. CONCLUSIONS: Various methods of EUS-guided transmural access to bile ducts improves endotherapy outcomes of patients with biliary obstruction. Endoscopic transmural access is highly effective and associated with an acceptable number of complications.

Early endoscopic treatment of symptomatic pancreatic necrotic collections.

EUS-guided transmural endoscopic drainage is commonly used in the treatment of WOPN in the late phase of ANP. The role of endoscopic intervention remains unclear in the early phase of ANP. This study aimed to prospectively evaluate early endoscopic treatment of ANCs compared with endoscopic drainage of WOPN. Overall, 71 patients with ANP who underwent transmural endoscopic drainage for necrotic collections were included. Endoscopic intervention was performed within the first four weeks of ANP in 25 (35.21%) patients with ANC (Group 1) and in 46 (64.79%) patients after four weeks since the onset of ANP with WOPN (Group 2). The overall mean age of patients was 49.9 (22-79) years and 59 of them were males. The mean time of active drainage and duration of total endoscopic treatment was 26.8 and 16.9 days (P = 0.0001) and 270.8 and 164.2 days (P = 0.0001) in Groups 1 and 2, respectively. The average total number of endoscopic interventions was 9.5 and 4.5 in Groups 1 and 2, respectively (P = 0.0001). The clinical success rate, frequency of complications of endoscopic interventions, long-term success rate, and recurrence rate were not significantly different between the groups (P > 0.05 for each). Transmural endoscopic drainage is effective method of treatment of early ANCs within the first four weeks of ANP. However, compared with endoscopic intervention in WOPN, more interventions and longer duration of drainage are required.

Transrectal endoscopic drainage with vacuum-assisted therapy in patients with anastomotic leaks following rectal cancer resection.

BACKGROUND: Surgery is the gold standard for the treatment of malignant tumors of the rectum. Intestinal anastomotic leakage remains a serious complication of colorectal surgery. The efficacy and safety of transrectal endoscopic drainage by vacuum therapy in patients with intestinal anastomotic leakage after surgical treatment of middle and distal rectal tumors were assessed. METHODS: Prospective analysis of treatment outcomes among patients undergoing surgery for middle and distal rectal tumors at the Department of General, Gastroenterological, and Oncological Surgery of the Ludwik Rydygier Collegium Medicum in Bydgoszcz and Nicolaus Copernicus University in Torun from 2016 to 2019 was conducted. RESULTS: Seventy-nine patients with middle and distal rectal tumors underwent laparoscopic resection. Intestinal anastomotic leak was identified in 18 (22.79%) patients [all men, mean age 61.39 (43-86) years] during the postoperative period. Primary protective ileostomy was performed in 8/18 (44.44%) patients. All 18 patients were treated with endoluminal vacuum therapy via transrectal endoscopic drainage. The mean time from surgery to the diagnosis of leakage and initiation of endoscopic treatment was 16 (3-728) days. The mean number of endoscopic procedures per patient was 6 (1-11). The mean duration of endoscopic treatment was 22 (4-43) days. Complications of endotherapy occurred in 2/18 (11.11%) patients treated endoscopically for bleeding from the abscess cavity. Success of endoluminal vacuum therapy was achieved in 17/18 (94.44%) patients. Moreover, 5/18 (27.78%) patients required ileostomy during the endoscopic treatment. The mean follow-up period was 368 (118-724) days. Long-term success of transrectal endoscopic drainage using vacuum-assisted therapy was achieved in 15/18 (83.33%) patients. CONCLUSIONS: Endoscopic rectal drainage using vacuum-assisted therapy is an effective and safe minimally invasive treatment in patients with intestinal anastomotic leaks following resection procedures within the middle and distal rectum.

The Role of Lumen-Apposing Metal Stents in Transmural Endoscopic Drainage of Postinflammatory Pancreatic and Peripancreatic Fluid Collections.

Rapid development of advanced gastrointestinal endoscopic techniques contributed to the appearance of new biomedical materials including polymers, which are used for the production of different types of endoprostheses. Endotherapy (ET) of postinflammatory pancreatic and peripancreatic fluid collections (PPFCs) with the use of lumen-apposing metal stent (LAMS) is an effective method of treatment. This paper describes the high efficacy of ET and its potential complications, which are mostly related to the design of the LAMS used. The high efficacy of LAMS in the transmural drainage of PPFCs is associated with lower safety of treatment. Complications of ET presented in the manuscript are mainly related to endoprosthesis' construction. This paper presents possible directions of development in the field of transmural LAMSs, which in the future may contribute to the invention of an innovative type of LAMS based on new biomedical technologies. Possibly, subsequent novel endoprosthesis projects, based on the above results, will be able to meet the current needs and requirements associated with endoscopic transmural drainage procedures in cases of postinflammatory PPFCs. The ultimate goal is to improve safety of minimally invasive techniques for treatment of the local consequences of pancreatitis.

Serious Complications of EUS-Guided Hepaticoesophagostomy due to Transmural Stent Migration.

Thoracic complications, such as biliopleural fistula and bile leaking into the right pleural cavity, are serious adverse events of transmural endoscopic ultrasound- (EUS-) guided biliary drainage involving EUS-guided hepaticoesophagostomy (EUS-HES). In this article, the authors present endoscopic treatment of biliopleural fistula as a serious thoracic complication of EUS-HES. The authors highlight key components of EUS-guided transmural biliary drainage and their experience with particular emphasis on endoscopic treatment of thoracic complications.

Outcomes and limitations of endoscopic ultrasound-guided hepaticogastrostomy in malignant biliary obstruction.

BACKGROUND: Transpapillary biliary drainage in ERCP is an established method for symptomatic treatment of patients with unresectable malignant biliary obstruction. Percutaneous transhepatic biliary drainage frequently remains the treatment of choice when the transpapillary approach proves ineffective. Recently, EUS-guided extra-anatomical anastomoses of bile ducts to the gastrointestinal tract have been reported as an alternative to percutaneous biliary drainage. To assess the usefulness of extra-anatomical intrahepatic biliary duct anastomoses to the gastrointestinal tract as endotherapy for unresectable malignant biliary obstruction and to determine factors affecting the efficacy of treatment. METHODS: A prospective analysis of the treatment results of all patients with unresectable biliary obstruction treated with EUS-guided hepaticogastrostomy at our institution in the years 2016-2019. RESULTS: Transmural intrahepatic biliary drainage (EUS-guided hepaticogastrostomy) was performed due to the ineffectiveness of ERCP in 53 patients (38 males, 15 females; mean age 74.66 [56-89] years) with unresectable biliary obstruction. Technical success of EUS-guided hepaticogastrostomy was achieved in 52/53 (98.11%) patients. Complications of endoscopic treatment were observed in 10/53 (18.87%) patients. Clinical success of EUS-guided hepaticogastrostomy was achieved in 46/53 (86.79%) patients. Bismuth type II-IV cholangiocarcinoma, hepatic metastases, ascites, suppurative cholangitis, and high blood bilirubin levels exceeding 30 mg/dL were independent factors for increased complications and inefficacy of EUS-guided hepaticogastrostomy. CONCLUSIONS: In the event of transpapillary biliary drainage proving ineffective, extra-anatomical anastomoses of intrahepatic bile ducts to the gastrointestinal tract provide an effective method for the treatment of patients with malignant biliary obstruction.

High levels of reactive oxygen species in pancreatic necrotic fluid of patients with walled-off pancreatic necrosis.

INTRODUCTION: Walled-off pancreatic necrosis (WOPN) is a life-threatening, late complication of acute pancreatitis, in which a fluid collection containing necrotic material is formed. Infection of the fluid collection significantly increases the mortality of patients with WOPN. AIM: To examine the levels of oxidative stress markers in the pancreatic necrotic fluid (PNF) and serum of patients with sterile and infected WOPN. MATERIAL AND METHODS: Thirty-three adult patients with sterile WOPN and 14 with infected WOPN, as well as 31 patients with mild AP, were included in this study. Concentrations of oxidative stress markers (8-isoprostane, protein carbonyl groups, and 8-hydroxyguanine) were measured in the PNF and serum of patients with sterile and infected WOPN. RESULTS: High concentrations of all measured oxidative stress markers in PNF, but not in serum, were detected in patients with WOPN. Additionally, oxidative stress markers in PNF were significantly increased in patients with infected as compared to sterile WOPN. The serum high sensitive C-reactive protein (hsCRP) concentrations showed the highest correlation with PNF oxidative stress marker levels. Receiver operating characteristics (ROC) curve analysis confirmed that serum hsCRP could be a good predictor of WOPN infection. CONCLUSIONS: Oxidative stress is associated with WOPN development; infection of PNF worsens the course of WOPN, possibly via increased production of reactive oxygen species; and serum hsCRP concentrations seem to be a good, noninvasive indicator of PNF infection.

The Role of Endoscopic Transpapillary Stenting of the Main Pancreatic Duct during the Endoscopic Treatment of Pancreatic Fluid Collections.

Endotherapy is a recognized, widely available, and minimally invasive treatment method for pancreatic fluid collections (PFCs) formed in the course of acute pancreatitis (AP). The use of endoscopic techniques in the treatment of main pancreatic duct (MPD) disruption due to AP remains unclear. In this article, a comprehensive review of current literature referencing our observations was performed to identify publications on the role of MPD stenting in patients undergoing endoscopic drainage of PFCs resulting from AP. In this paper, we attempt to clarify this most controversial aspect of endotherapy for PFCs based on existing knowledge and our own experience regarding the endoscopic treatment of AP sequelae. Endoscopic retrograde pancreatography should be performed in all patients undergoing endoscopic drainage of walled-off pancreatic necrosis to assess the integrity of the main pancreatic duct and to implement endotherapy if pancreatic duct disruption is detected. Passive transpapillary drainage is an effective method for treating MPD disruption in the course of necrotizing AP and is one of the key components of endoscopic therapy for local pancreatic necrosis. Conversely, in patients with pancreatic pseudocysts, passive transpapillary drainage reduces the effectiveness of endoscopic treatment and should not be used even in cases of MPD disruption during transmural drainage of pancreatic pseudocysts. In conclusion, the use of transpapillary drainage should depend on the type of the PFC. This conclusion is of great clinical importance, as it can help improve the results of pancreatic endotherapy for fluid collections resulting from AP.

Challenges Encountered during the Treatment of Acute Mesenteric Ischemia.

RESULTS: Acute ischemia of the bowel mesentery was diagnosed in 41 patients (27 women and 14 men; mean age, 65.4 years). All patients underwent laparotomy. For 13 (31.71%) patients, surgery was performed within the first 24 hours of the clinical symptom onset. Mesenteric artery embolectomy without intestine resection was performed for 7 (17.07%) patients. Partial intestine resection due to necrosis was performed for 21 (51.22%) patients. Exploratory laparotomy without a therapeutic procedure was performed for 13 (31.71%) patients. Fifteen (36.59%) patients were discharged home in good general condition. Twenty-six (63.41%) patients died. The time from the clinical symptom onset until intervention exceeded 24 hours for all patients who died. Surgery within the first 24 hours reduced mortality associated with acute mesenteric ischemia (P = 0.001). Female sex, age older than 65 years, obesity (body mass index > 30), diabetes, chronic kidney disease, and smoking were adverse prognostic factors for increased mortality for patients with acute bowel ischemia. CONCLUSION: The time from clinical symptoms to acute mesenteric ischemia treatment was the main prognostic factor and helped determine appropriate management. Early diagnosis and rapid intervention improved treatment outcomes and survival.