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Veterinary Surgery : VS Jun 2024To determine the feasibility of open cholangioscopy using disposable flexible endoscopes in canine cadavers and describe the surgical approach.
OBJECTIVE
To determine the feasibility of open cholangioscopy using disposable flexible endoscopes in canine cadavers and describe the surgical approach.
STUDY DESIGN
Ex vivo experimental cadaveric study.
SAMPLE POPULATION
Eight canine cadavers.
METHODS
Cadavers ranging from 5.8 to 43.8 kg underwent open transcholecystic cholangioscopy using a disposable flexible endoscope with a 3.8 mm outer diameter and 1.2 mm working channel and the surgical approach was described. The most distal anatomical region of the biliary tree towards the duodenal papilla that was visualized with the endoscope was recorded in each cadaver. A 2.7 mm rigid endoscope and a 1.9 mm flexible endoscope were also trialed and findings recorded. Endoscopic tools were trialed and their usage recorded.
RESULTS
The disposable flexible endoscope was feasible for visualization of the junction of the common bile duct, cystic duct, and hepatic ducts in all eight dogs. Cholangioscopy using a 2.7 mm rigid endoscope did not provide further distal visualization. The 1.9 mm flexible endoscope was able to traverse down to the level of the major duodenal papilla in a 43.8 kg cadaver. Use of certain endoscopic tools can be considered through the disposable flexible endoscope although fluid instillation was affected.
CONCLUSION
A 3.8 mm disposable flexible endoscope could be placed through an open transcholecystic approach to provide intraluminal endoscopic evaluation up to the level of the junction of the common bile duct, cystic duct, and hepatic ducts in dogs without cholecystic disease.
CLINICAL SIGNIFICANCE
Open transcholecystic cholangioscopy with a disposable flexible endoscope could provide a low-cost diagnostic and therapeutic tool in cases of obstructive biliary disease up to the level of the common bile duct.
PubMed: 38940529
DOI: 10.1111/vsu.14124 -
Molecular Therapy. Nucleic Acids Jun 2024Small interfering RNAs (siRNAs) are revolutionizing the treatment of liver-associated indications. Yet, robust delivery to extrahepatic tissues remains a challenge....
Small interfering RNAs (siRNAs) are revolutionizing the treatment of liver-associated indications. Yet, robust delivery to extrahepatic tissues remains a challenge. Conjugating lipids (e.g., docosanoic acid [DCA]) to siRNA supports extrahepatic delivery, but tissue accumulation remains lower than that achieved in liver by approved siRNA therapeutics. Early evidence suggests that functionalizing DCA with a head group (e.g., phosphatidylcholine [PC]) may enhance delivery to certain tissues. Here, we report the first systematic evaluation of the effect of PC head group chemistry on the extrahepatic distribution of DCA-conjugated siRNAs. We show that functionalizing DCA with a PC head group enhances siRNA accumulation in heart, muscle, lung, pancreas, duodenum, urinary bladder, and fat. Varying the size of the linker between the phosphate and choline moiety of the PC head group altered the extrahepatic accumulation of siRNA, with the optimal linker length being different for different tissues. Increasing PC head group valency also improved extrahepatic accumulation in a tissue-specific manner. This study demonstrates the structural impact of the PC moiety on the biodistribution of lipid-conjugated siRNA and introduces multiple novel PC variants for the chemical optimization of DCA-conjugated siRNA. These chemical variants can be used in the context of other lipids to increase the repertoire of conjugates for the extrahepatic distribution of siRNAs.
PubMed: 38938759
DOI: 10.1016/j.omtn.2024.102230 -
The International Journal of... Jun 2024Thrombomodulin (TM) exerts anticoagulant and anti-inflammatory effects to improve the survival of patients with septic shock. Heat stroke resembles septic shock in many...
BACKGROUND
Thrombomodulin (TM) exerts anticoagulant and anti-inflammatory effects to improve the survival of patients with septic shock. Heat stroke resembles septic shock in many aspects. We tested whether TM would improve cognitive deficits and related causative factors in heat-stressed mice.
METHODS
Adult male mice were exposed to HS (33 oC 2h daily for 7 consecutive days) to induce cognitive deficits. Recombinant human soluble thrombomodulin (TM, 1 mg/kg, i.p.) was administered immediately after the first HS trial and then once daily for 7 consecutive days. We performed the Y-maze, novel objective recognition, and passive avoidance tests to evaluate cognitive function. Plasma levels of lipopolysaccharide, high-mobility group box 1 (HMGB1), coagulation parameters, and both plasma and tissue levels of inflammatory and oxidative stress markers were measured biochemically. The duodenum and hippocampus sections were immunohistochemically stained. The intestinal and blood-brain barrier permeability were determined.
RESULTS
Compared to controls, HS mice treated with TM had lesser extents of cognitive deficits, exacerbated stress reactions, gut barrier disruption, endotoxemia, blood-brain barrier disruption, and inflammatory, oxidative, and coagulatory injury to heart, duodenum, and hippocampal tissues, and increased plasma HMGB1. In addition to reducing cognitive deficits, TM therapy alleviated all the abovementioned complications in heat-stressed mice.
CONCLUSIONS
The findings suggest that heat stress can lead to exacerbated stress reactions, endotoxemia, gut barrier disruption, blood-brain barrier disruption, hippocampal inflammation, coagulopathy, and oxidative stress, which may act as causative factors for cognitive deficits. Thrombomodulin, an anti-inflammatory, antioxidant, and anti-coagulatory agent, inhibited heat stress-induced cognitive deficits in mice.
PubMed: 38938182
DOI: 10.1093/ijnp/pyae027 -
The American Journal of Surgical... Jun 2024The guidelines recently recognized the intra-ampullary papillary tubular neoplasm (IAPN) as a distinct tumor entity. However, the data on IAPN and its distinction from...
The guidelines recently recognized the intra-ampullary papillary tubular neoplasm (IAPN) as a distinct tumor entity. However, the data on IAPN and its distinction from other ampullary tumors remain limited. A detailed clinicopathologic analysis of 72 previously unpublished IAPNs was performed. The patients were: male/female=1.8; mean age=67 years (range: 42 to 86 y); mean size=2.3 cm. Gross-microscopic correlation was crucial. From the duodenal perspective, the ampulla was typically raised symmetrically, with a patulous orifice, and was otherwise covered by stretched normal duodenal mucosa. However, in 6 cases, the protrusion of the intra-ampullary tumor to the duodenal surface gave the impression of an "ampullary-duodenal tumor," with the accurate diagnosis of IAPN established only by microscopic correlation illustrating the abrupt ending of the lesion at the edge of the ampulla. Microscopically, the preinvasive component often revealed mixed phenotypes (44.4% predominantly nonintestinal). The invasion was common (94%), typically small (mean=1.2 cm), primarily pancreatobiliary-type (75%), and showed aggressive features (lymphovascular invasion in 66%, perineural invasion in 41%, high budding in 30%). In 6 cases, the preinvasive component was pure intestinal, but the invasive component was pancreatobiliary. LN metastasis was identified in 42% (32% in ≤1 cm IAPNs). The prognosis was significantly better than ampullary-ductal carcinomas (median: 69 vs. 41 months; 3-year: 68% vs. 55%; and 5-year: 51% vs. 35%, P=0.047). Unlike ampullary-duodenal carcinomas, IAPNs are often (44.4%) predominantly nonintestinal and commonly (94%) invasive, displaying aggressive features and LN metastasis even when minimally invasive, all of which render them less amenable to ampullectomy. However, their prognosis is still better than that of the "ampullary-ductal" carcinomas, with which IAPNs are currently grouped in CAP protocols (while IAPNs are kindreds of intraductal tumors of the pancreatobiliary tract, the latter represents the ampullary counterpart of pancreatic adenocarcinoma/cholangiocarcinoma).
PubMed: 38938087
DOI: 10.1097/PAS.0000000000002275 -
British Journal of Cancer Jun 2024Pancreatoduodenectomy is the only cure for cancers of the pancreas and the periampullary region but has considerable operative complications and uncertain prognosis. Our...
BACKGROUND
Pancreatoduodenectomy is the only cure for cancers of the pancreas and the periampullary region but has considerable operative complications and uncertain prognosis. Our goal was to analyse temporal improvements and provide contemporary population-based benchmarks for outcomes following pancreatoduodenectomy.
METHODS
We empanelled a cohort comprising all patients in Sweden with pancreatic or periampullary cancer treated with pancreatoduodenectomy from 1964 to 2016 and achieved complete follow-up through 2016. We analysed postoperative deaths and disease-specific net survival.
RESULTS
We analysed 5923 patients with cancer of the pancreas (3876), duodenum (444), bile duct (504), or duodenal papilla (963) who underwent classic (3332) or modified (1652) Whipple's procedure or total pancreatectomy (803). Postoperative deaths declined from 17.2% in the 1960s to 1.6% in the contemporary time period (2010-2016). For all four cancer types, median, 1-year and 5-year survival improved substantially over time. Among patients operated between 2010 and 2016, 5-year survival was 29.0% (95% confidence interval (CI): 25.5, 33.0) for pancreatic cancer, 71.2% (95% CI: 62.9, 80.5) for duodenal cancer, 30.8% (95% CI: 23.0, 41.3) for bile duct cancer, and 62.7% (95% CI: 55.5, 70.8) for duodenal papilla cancer.
CONCLUSION
There is a continuous and substantial improvement in the benefit-harm ratio after pancreatoduodenectomy for cancer.
PubMed: 38937622
DOI: 10.1038/s41416-024-02757-w -
Journal of Agricultural and Food... Jun 2024Hemoglobin is an excellent source of iron supplements, and its hydrolyzate spontaneously binds iron during digestion and promotes iron absorption in vivo. However, the...
Hemoglobin is an excellent source of iron supplements, and its hydrolyzate spontaneously binds iron during digestion and promotes iron absorption in vivo. However, the underlying mechanisms of what peptides bind and how they bind iron ions remain unclear. This study prepared the porcine hemoglobin hydrolyzate through enzymatic hydrolysis and acid treatment and investigated the mechanisms of hemoglobin hydrolyzate on iron absorption through the determination of iron levels in dietary intervention mice, iron binding site analyses, peptide digestion analyses, molecular simulation docking, and INT407 cell validation. The results showed that ingestion of the hemoglobin hydrolyzate diets increased iron levels in the blood of mice, accompanied by the upregulation of duodenal iron circulation-related genes such as ferritin, PCBP1, and HP. Carboxyl, imidazole groups, and aromatic amino acid residues were iron binding sites of hemoglobin hydrolyzate during digestion. VDEVGGEA and VDEVGGE were found to involve the spontaneous and efficient binding of hemoglobin hydrolyzate to iron ions in the intestinal cavity. In particular, the DEVGGE peptide was the typical sequence for hemoglobin hydrolytic peptides to exert iron binding activity.
PubMed: 38935870
DOI: 10.1021/acs.jafc.4c00364 -
Gut Microbes 2024The microbiota significantly impacts digestive epithelium functionality, especially in nutrient processing. Given the importance of iron for both the host and the...
The microbiota significantly impacts digestive epithelium functionality, especially in nutrient processing. Given the importance of iron for both the host and the microbiota, we hypothesized that host-microbiota interactions fluctuate with dietary iron levels. We compared germ-free (GF) and conventional mice (SPF) fed iron-containing (65 mg/Kg) or iron-depleted (<6 mg/Kg) diets. The efficacy of iron privation was validated by iron blood parameters. Ferritin and Dmt1, which represent cellular iron storage and transport respectively, were studied in tissues where they are abundant: the duodenum, liver and lung. When the mice were fed an iron-rich diet, the microbiota increased blood hemoglobin and hepcidin and the intestinal ferritin levels, suggesting that the microbiota helps iron storage. When iron was limiting, the microbiota inhibited the expression of the intestinal Dmt1 transporter, likely via the pathway triggered by Hif-2α. The microbiota assists the host in storing intestinal iron when it is abundant and competes with the host by inhibiting Dmt1 in conditions of iron scarcity. Comparison between duodenum, liver and lung indicates organ-specific responses to microbiota and iron availability. Iron depletion induced temporal changes in microbiota composition and activity, reduced α-diversity of microbiota, and led to becoming particularly more abundant after 60 days of privation. By inoculating GF mice with a simplified bacterial mixture, we show that the iron-depleted host favors the gut fitness of .
Topics: Animals; Mice; Gastrointestinal Microbiome; Iron, Dietary; Cation Transport Proteins; Liver; Duodenum; Hepcidins; Ferritins; Germ-Free Life; Host Microbial Interactions; Lung; Iron; Basic Helix-Loop-Helix Transcription Factors; Bacteria; Mice, Inbred C57BL; Hemoglobins; Male
PubMed: 38935764
DOI: 10.1080/19490976.2024.2361660 -
Current Opinion in Gastroenterology Jun 2024Although the mucosal barrier serves as a primary interface between the environment and host, little is known about the repair of acute, superficial lesions or deeper,...
PURPOSE OF REVIEW
Although the mucosal barrier serves as a primary interface between the environment and host, little is known about the repair of acute, superficial lesions or deeper, persistent lesions that if not healed, can be the site of increased permeability to luminal antigens, inflammation, and/or neoplasia development.
RECENT FINDINGS
Studies on acute superficial lesions have been sparse in the past year, with more focus given to novel mechanisms of mucosal protection, and the way in which mature epithelial cells or committed stem cells dedifferentiate, reprogram, proliferate, and then regenerate the gastroduodenal mucosa after injury. For this, adenoviral therapy showed organ specific targeting with mRNA and protein expression of effectors to protect against mucosal injury and ulceration. A large database of plant-based agents known to protect against injury and ulceration was published, along with studies using plant-based compounds delivered with alginates, polysaccharide/gel floating rafts, or incorporated into nanoparticles or green carbon dots to improve targeting and retention at the ulcerated lesion. With RNA technology developing rapidly, particularly single-cell RNA sequencing, important and novel data was forthcoming on mucosal regeneration. In particular, the role of interleukin-17 hub proteins in mucosal healing was highlighted. The presence and role of injury reserve cells was determined, as was the composition of ligand gradients for cell differentiation in both stomach and duodenum. The role of amphiregulin in parietal cell differentiation from lineage-restricted stem cells and the Yap1 gene signature in metaplasia vs. healing ulcers were of particular importance. Additionally, studies unveiled the important role of mesenchymal stromal cells in differentiation and repair mechanisms, in Muse cells as an exciting new therapy for mucosal repair after injury, and the role of sympathetic neurons in activating the immune system to regulate mucosal repair mechanisms.
SUMMARY
Recent studies highlight novel mechanisms that promote mucosal regeneration after injury of the gastroduodenal mucosa.
PubMed: 38935320
DOI: 10.1097/MOG.0000000000001049 -
Emergency Radiology Jun 2024Ectopic varices account for 5% of variceal bleedings and occur outside the gastro-esophageal region. This review evaluates the efficacy of transjugular intrahepatic... (Review)
Review
Ectopic varices account for 5% of variceal bleedings and occur outside the gastro-esophageal region. This review evaluates the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) for ectopic variceal management. A comprehensive search through PubMed, Scopus, Web of Science, and Embase was conducted until January 16, 2023, using relevant keywords. Case reports and case series with fewer than 10 patients on TIPS for ectopic variceal management were included. The quality assessment followed the Joanna Briggs Institute checklist for case reports. This systematic review evaluated 43 studies involving 50 patients with ectopic varices undergoing TIPS. Patients had a mean age of 54.3 years, half were female, and two were pregnant. Alcoholic liver disease (48%) and hepatitis C infection (26%) were common causes of portal hypertension. Ascites and splenomegaly were reported in 32% and 28% of the patients, respectively. Rectal, oral, and stomal variceal bleeding accounted for 62%, 16%, and 22% of the patients, respectively. Ectopic varices were mainly located in the duodenum (28%) and rectum (26%) regions. Complications affected 42% of the patients, re-bleeding in eleven and hepatic encephalopathy in seven. The follow-up lasted 12 months on average, and finally, 5 received a liver transplant. Mortality post-TIPS was 18%. Despite complications and a notable mortality rate, favorable outcomes were observed in almost half of the patients with ectopic variceal bleeding managed with TIPS. Further research is warranted to refine strategies and improve patient outcomes.
PubMed: 38935315
DOI: 10.1007/s10140-024-02258-6 -
Journal of Inflammation Research 2024Significant gastrointestinal hemorrhages, resulting from long-term compression of the duodenum by a hepatic pseudoaneurysm (HAPA), is an extremely rare condition. In...
AIM
Significant gastrointestinal hemorrhages, resulting from long-term compression of the duodenum by a hepatic pseudoaneurysm (HAPA), is an extremely rare condition. In fact, when the pseudoaneurysm is small in diameter, diagnosis can be particularly challenging. Timely and effective diagnosis and treatment is therefore of great significance, and in this case, endoscopy, combined with intravascular therapy, can provide an effective approach, especially since it removes the need for surgery while yielding favorable outcomes.
CASE SUMMARY
A 75-year-old old man presented to the hospital's emergency department with hematemesis and black stool. Despite conservative treatments such as "acid suppression, fluid resupply, hemostasis and blood transfusion", no significant improvement was noted. Emergency gastroscopy subsequently revealed an ulcer in the duodenal bulb (Figure 1), with an exposed thrombotic head and active bleeding on the surface. In addition, abdominal computed tomography (Figure 2) showed no obvious HAPA manifestations. After unsuccessful endoscopic hemostasis, angiography was performed (Figure 3) and a pseudotumor-like dilatation measuring 5.56 mm in diameter was found at the distal end of the proximal branch vessel of the common hepatic artery. Following spring coil embolization (Figure 4), the patient's condition improved and he was discharged from the hospital, with a follow-up after six months showing no signs of recurrence or complications.
CONCLUSION
Duodenal ulcer hemorrhages due to small hepatic pseudoaneurysms are very rare, with endoscopic intervention being effective for such cases.
PubMed: 38933359
DOI: 10.2147/JIR.S467969