Duct Injury Research Articles

Treatment of walled-off pancreatic necrosis.

To review the current management of walled-off pancreatic necrosis (WOPN). The management of WOPN has evolved. Many collections do not require intervention and may resolve over time. Nutritional support and treatment of infection are two critical components of medical management. For collections requiring drainage, minimally invasive endoscopic therapies now play a primary role. Endoscopic transmural puncture with stent placement may provide access for drainage and decompression. More complex collections may require transluminal instrumentation with lavage, debridement, and necrosectomy. Concurrent pancreatic duct injuries including strictures, leaks, and disconnections are very common. Addressing the pancreatic ductal injury is a key component in the long-term success of management strategies. Providing high-level care for patients requires a multidisciplinary approach with providers specialized in the management of severe acute pancreatitis and associated complications. Minimally invasive management strategies improve the outcomes for patients with WOPN. Close follow-up, medical therapy, and nutritional support are required for most patients. Endoscopic transmural drainage and necrosectomy are the primary approaches for collections requiring intervention. Protocols for endoscopic drainage are being refined to reduce side effects and decrease the number of interventions required for resolution.

Frontal Sinus Fractures: Management and Complications.

Frontal sinus fractures are relatively rare maxillofacial injuries (only 5-15% of all facial fractures). The appropriate management of frontal sinus fracture and associated pathology is controversial. Diagnosis and treatment of frontal sinus fractures has improved with the advances of high-resolution computed tomography technology. Treatment of frontal sinus fractures depends on several factors, including contour deformity of anterior table; the presence of CSF leak or air-fluid level in the sinus, likelihood of nasofrontal duct obstruction, and degree of displacement of posterior table. Nasofrontal duct patency should be checked if fracture pattern is highly suspicious of ductal injury. Cranialization is performed in cases of severely comminuted posterior wall fracture. Long-term complication of frontal sinus fracture can occur up to 10 years after initial injury or intervention; so, judicious long-term follow-up is warranted. This article presents the management and complications of frontal sinus fractures.

Emodin attenuates adenosine triphosphate‑induced pancreatic ductal cell injury in vitro via the inhibition of the P2X7/NLRP3 signaling pathway.

Acute pancreatitis (AP) is an inflammatory disease with high morbidity and mortality rates. Pancreatic ductal cells are the most susceptible of all cell types that are exposed to the noxious stimuli of pancreatitis. Our previous studies demonstrated that emodin, a natural product extracted from Rheum palmatum L., protected pancreatic acinar cells from injutyh due to its anti‑inflammatory activity. In the present study, in order to investigate the protective effects and molecular mechanisms of action of emodin on injured pancreatic ductal cells, an adenosine triphosphate (ATP)‑induced model of cell injury was established using the human pancreatic ductal epithelial cell line, HPDE6‑C7. The results revealed that emodin attenuated ATP‑induced HPDE6‑C7 cell injury by decreasing the levels of inflammatory factors, including interleukin (IL)‑1β and IL‑18. Furthermore, emodin significantly downregulated the protein levels of purinergic receptor P2X, ligand‑gated ion channel, 7 (P2X7), NOD‑like receptor protein 3 (NLRP3), apoptosis‑associated speck‑like protein containing a CARD (ASC) and caspase‑1 in the injured HPDE6‑C7 cells. The results also indicated that emodin attenuated HPDE6‑C7 cell injury at least partially through the inhibition of the P2X7/NLRP3 signaling pathway. The protective effects of emodin were abrogated upon pre‑treatment with P2X7 overexpression plasmid, which further confirmed that the P2X7 signaling pathway is the drug target of the effects of emodin against ATP‑induced pancreatic ductal cell injury. Collectively, the findings of this study demonstrate that emodin attenuates ATP‑induced pancreatic ductal cell injury in AP mainly through the inhibition of the P2X7/NLRP3 signaling pathway. This study suggests that emodin may be further developed for its application in future medical therapy.

Intraoperative detection of aberrant biliary anatomy via intraoperative cholangiography during laparoscopic cholecystectomy.

Laparoscopic cholecystectomy (LC) is the standard of treatment for symptomatic cholelithiasis. Although intraoperative cholangiography (IOC) is widely used as an adjunct to LC, there is still no worldwide consensus on the value of its routine use. Anatomical studies have shown that variations of the biliary tree are present in approximately 35% of patients with variations in right hepatic second-order ducts being especially common (15-20%). Approximately, 70-80% of all iatrogenic bile duct injuries are a consequence of misidentification of biliary anatomy. The purpose of this study was to assess the adequacy of and the reporting of IOCs during LC. IOCs obtained from 300 consecutive LCs between July 2014 and July 2016 were analysed retrospectively by two surgical trainees and confirmed by a radiologist. Biliary tree anatomy was classified from IOC films as described by Couinaud (1957) and correlated with documented findings. The accuracy of intraoperative reporting was assessed. Biliary anatomy was correlated to clinical outcome. A total of 95% of IOCs adequately demonstrated biliary anatomy. Aberrant right sectoral ducts were identified in 15.2% of the complete IOCs, and 2.6% demonstrated left sectoral or confluence anomalies. Only 20.4% of these were reported intraoperatively. Bile leaks occurred in two patients who had IOCs (0.73%) and two who did not (7.4%). Surgeons generally demonstrate biliary anatomy well on IOC but reporting of sectoral duct variation can be improved. Further research is needed to determine whether anatomical variation is related to ductal injury.

A Functional Approach to Posttraumatic Salivary Fistula Treatment: The Use of Botulinum Toxin.

This manuscript highlights key aspects regarding the practical use of botulinum toxin for the conservative nonsurgical treatment of a rarely encountered, but significant posttraumatic complication-the parotid salivary fistula. It adds information to the scarce existing literature on the subject. The authors outline the main differences between postoperative and trauma-related parotid injury regarding salivary fistula treatment. A total of 6 patients with trauma-related salivary fistulas have been treated by Abobotulinum toxin A injections over the course of 5 years. The technique is detailed, describing the doses used in the presence of parenchyma and duct injuries, the location and number of injection points in relation to the wound pattern. The results were favorable, leading to the healing of the salivary fistulas in all patients, with 1 injection session, without additional conservative treatment. In our experience, the use of botulinum toxin is of great benefit for treating salivary fistulas in a traumatic context.

The Stensen's duct line: A landmark in parotid duct and gland injury and surgery. A prospective anatomical, clinical and radiological study

IntroductionThe parotid duct (PD) is often involved in parotid gland diseases. A skin landmark could help the surgeon to locate its position. The parotid duct line (PDL) joins the tragus-antitragus point to the middle of the half upper lip. The aim of this study was to assess and scientifically validate this landmark. MethodsA monocentric prospective anatomical, clinical and radiological study was conducted. Six fresh cadavers’ PD were dissected. A subcutaneous flap was performed and the PD's position spotted by needle checking through the skin. 10 subjects with parotid obstructive symptoms were included for sialendoscopy, which light through the skin revealed the PDL's position. MRI was conducted on 20 PDs. The radiologist virtually drew the PDL and did a 3D reconstruction of the PD. The distance from the PDL to the PD was measured. ResultsAnatomical study: 2 PDs were on the PDL, 2 under and 2 over.Sialendoscopic study: 6 PDs were on the PDL (60%), 3 under and 1 over. MRI study: 13 over 20 PDs crossed the PDL (65%). Maximum mean distance from the PD was 10.44 mm [5.01–15.87] and minimum mean distance from the PD was 2.42 mm [0–5.75]. DiscussionThis study sought to assess the relevance of the PDL, which is not parallel to the PD that runs a «S-Shape» curve when crossing the PDL. It could be used when evaluating a potential ductal injury in trauma management and when locating proximal parotid lithiasis during sialendoscopy.

Bile duct injuries and systemic approach to the treatment

Aim.Present a program of examination and treatment of patients with biliary duct injury, corresponding to the level of the international protocol and modern requirements for the quality of medical care.Material and methods.The results of examination and treatment of 77 patients with bile ducts injuries are analyzed. The analysis of the main surgical interventions for the elimination of bile ducts injuries is given: reconstructive operations in 44.3% of patients, recovery operations – in 36.7% and external drainage – in 19%.Results.A program approach has been developed to assist patients with bile duct injuries in civil health care at various levels of surgical care.Conclusions.The implementation of this program provides timely diagnosis of damage to the bile duct and minimizing the number of postoperative complications at the second and third levels of surgical care. It was determined that a rational approach to reduce the number of injuries of the bile ducts is their prevention by perfect adherence to the technique of surgical intervention on the organs of the upper floor of the abdominal cavity, and to reduce the number of negative consequences, the proposed algorithm for diagnosis and treatment.

Evidence of a microbial etiology for sialoliths.

Sialolithiasis is the primary etiology for parotid and submandibular swelling, potentially resulting in discomfort, bacterial infections, and hospitalization. The etiology of sialolith formation is unknown. Currently, the proposed etiologies range from inflammation, coalescence of organic molecules, sialomicrolith formation, pH changes, and biofilm formation. In this study, we performed a descriptive analysis of images obtained through electron microscopy of sialoliths. Based on our findings and descriptive analysis, we hypothesize that sialolith formation is likely multifactorial and begins with biofilm formation. Biofilm formation then triggers a host immune response, and it is the interaction of biofilm with host immune cells and calcium nanoparticles that forms the nidus and creates a favorable environment for calcium precipitation. Sialoliths were extracted from patients and imaged under light and scanning electron microscopy. Specimens for light microscopy were prepared using a diamond saw. Specimens for electron microscopy were freeze-fractured, thus providing an undisturbed view of the core of the sialolith. We were able to identify clear evidence of biofilm caves at the core of each sialolith. These biofilm caves were complex with the presence of bacteria and dehydrated extrapolysaccharide matrix, host cells (immune cells, platelets and erythrocytes), and calcium nanoparticles. The etiology of sialolith formation is likely multifactorial. We propose that biofilm formation within a single salivary gland or duct leads to local ductal injury, which results in the influx of host immune cells that interact with the biofilm and calcium nanoparticles, creating a scaffold upon which further calcium deposition can occur. NA Laryngoscope, 130:69-74, 2020.

Bile leak syndrome after laparoscopic cholecystectomy

Aim of the study was the assasement of surgical treatment results of patients with cholelithiasis, who had external or internal bile leakage (BL), for the optimization and improvement of diagnostic programme and surgical tactic of minimally invasive techniques usage. Materials and methods. Results of surgical treatment during the early postoperative period of patients with cholelithiasis, who underwent laparoscopic cholecystectomy (LC) were analysed. Results. In early post-operative period 67 (0,6%) patients, mean aged 56,9 ± 7,4 had BL. 54 (81,0%) of them were women, 13 (19,0%) were men. 21 (31,3%) patients underwent LC due to chronic cholecystitis, 46 (68,7%) patients had acute cholecystitis. In 54 (81,0%) cases there was drainage bile leakage, in 13 (19,0%) cases bile collection in abdominal cavity was identified several days after drains ejection, due to clinical manifestation and ultrasonography data. 23 (34,3%) patients were treated conservatively. Minimally invasive endoscopic manipulations, ultrasonography controlled percutaneous drainage and relaparotomy were effective in 35 (52,2%) patients, 9 (13,4%) patients underwent laparotomy with following surgical correction of BL. These patients had dense perivesical infiltrates, Mirizzi’s syndrome type I. 6 (9,0%) patients underwent laparotomy, abdominal cavity sanation and drainage. In 1 (1,5%) case partial right bile duct injury was identified, defect suturing and Vishnevsky common bile duct drainage. In 2 (3,0%) cases the cause of BL was more than 2/3 diameter injury of common bile duct. These patients underwent Roux-en-Y hepaticojejunostomy. Conclusion. Installation of drainage into the hepatic space and the right flank provide early diagnosis of postoperative complications, one of which is bile flow syndrome. Ultrasound examination of abdominal organs and endoscopic retrograde cholangiopancretography are performed to determine the cause and localization of the syndrome of the BL syndrome, depending on the volume of the BL. Repeated laparoscopy is indicated for the phenomena of bile peritonitis, significant accumulation of bile in the abdominal cavity. The complex usage of relaparoscopy, transduodenal endoscopic interventions and puncture techniques can significantly reduce the number of laparotomy operations to correct complications.

Surgical drainage versus repair in the treatment of distal common bile duct injury

Objective To compare the efficacy of surgical drainage versus repair in the treatment of iatrogenic injury of the distal common bile duct detected during operation, and to evaluate the effect of gastrobiliary duct drainage. Methods Patients with iatrogenic choledochal injury were divided into two groups: the drainage group (n=17) and the repair group (n=7). Data on the amounts of postoperative biliary and abdominal cavity drainage, gastrointestinal function recovery, the duration of biliary drainage and hospitalization were compared. Results When compared with the repair group, there were no significant differences in the amounts of postoperative biliary drainage [(310.0±112.0) vs. (264.0±144.0)ml] and abdominal cavity drainage [(42.0±25.0)ml vs. (125.0±195.0)ml)] (both P>0.05). However, gastrointestinal function recovery [(3.0±1.5)d vs. (4.7±2.0)d], durations of biliary drainage [(7.5±1.0)d vs. (12.7±5.4)d] and hospitalization [(9.5±1.5)d vs. (15.1±5.6)d] of the drainage group were significantly shorter than the repair group (P<0.05). No biliary strictures of cholangitis were detected in the two groups. Conclusion When compared with traditional repair, gastrobiliary drainage was a simpler, safer, and more effective therapeutic strategy for patients with iatrogenic distal common bile duct injury, and with a quicker recovery after treatment. Key words: Distal common bile duct; Iatrogenic injury; Gastrobiliary duct drainage

Hydrogen Peroxide-Assisted Endoscopic Necrosectomy

Pancreatic inflammation can result in varying degrees of transient and permanent pancreatic parenchymal or ductal injury. Pancreatic necrosis and pseudocyst formation may occur and can require endoscopic or surgical intervention. Hydrogen peroxide-assisted necrosectomy is an endoscopic technique for irrigation of walled off pancreatic collections to chemically debride solid components. An 84-year-old male with a medical history of gallstone pancreatitis post cholecystectomy complicated by sepsis, pseudocyst (17.2 cm x 9 cm) and end organ damage, experienced gram negative bacteremia from pseudocyst infection 4 weeks after his bout of pancreatitis. The patient underwent cystgastrostomy with endoscopic ultrasound, aspiration of purulent material, and lumen opposing (Axios) stent placement. Several necrosectomies were required due to the presence of solid necrotic material within the pseudocyst. The initial necrosectomy successfully cleared the stent of solid material and aspirated purulent fluid. Upon re-inspection at a 2 week interval, solid material was visualized and lavage of the pseudocyst with 2 weeks of enterally ingested “coca-cola” was attempted. A third inspection of the stent revealed re-occlusion with solid debris. Intra-procedurally, 120mL of 1.5% hydrogen peroxide solution lavage with mechanical debridement resulted in near complete evacuation of the pseudocyst cavity. The stent was removed and a 10 French x 7 cm pigtail was left to enable further drainage of the cavity. Patient's symptomatology resolved and repeat imaging confirmed collapse of the pseudocyst to 2.3 by 1.2 cm. The pigtail stent was removed and the patient remains asymptomatic. The use of hydrogen peroxide during pancreatic pseudocyst necrosectomy appears to aid in the chemical dissolution of solid necrotic material and facilitate resolution of pancreatic collections. We encourage scrupulous utilization of this technique as an aide during necrosectomies to collect further data on its absolute utility during endoscopic management of pancreatic pseudocycts.2112_A Figure 1. Endoscopic view of pancreatic pseudocyst through the lumen opposing stent visualizing extensive necrotic debris prior to lavage with a 1.5% solution of hydrogen peroxide.2112_B Figure 2. Endoscopic view of cystgastrostomy with solid necrotic debris extruding through the lumen opposing stent prior to debridement with a 1.5% solution of hydrogen peroxide.2112_C Figure 3. Endoscopic view of pancreatic pseudocyst through the lumen opposing stent visualizing successful debridement of solid necrotic material using a 1.5% solution of hydrogen peroxide.

Operative versus non-operative management of blunt pancreatic trauma: A systematic review

Introduction Motor vehicle crashes are common causes of blunt abdominal trauma in the 21st century. While splenic trauma occurs very frequently and thus there is a well-established treatment paradigm, traumatic pancreatic injuries are relatively infrequent, occurring in only 3–5% of traumas. This low incidence means physicians have reduced experience with this condition and there is still ongoing debate with regards to the best practice in managing pancreatic trauma. During severe trauma, the pancreas can be injured as a consequence of blunt and penetrating injury. This has an estimated mortality rate ranging from 9 to 34%. Methods A systematic review was performed using three scientific databases: Embase, Medline and Cochrane and in-line with the PRISMA statement. We included only articles published in English, available as full text and describing only adults. Keywords included: pancrea*, trauma, blunt, operative management and non-operative management. Results Three studies were found that directly compared operative versus non-operative management in blunt pancreatic trauma. Length of stay, mortality and rate of re-intervention were lower in the non-operative group compared to the operative group. However, the average grade of pancreatic injury was lower in the non-operative group compared to the operative group. Discussion Our results revealed that patients who undergo non-operative management tend to have lower grade of injuries and patients with higher grade of injury tend to be managed in an operative fashion. This could be likely due to the fact that higher grade of pancreatic injuries is often accompanied by other injuries such as hollow viscus injury and therefore require operative intervention. Conclusion Non-operative management is a safe approach for low-grade blunt pancreatic trauma without ductal injuries. However, more evidence is required to improve our understanding and treatment plans. We suggest a large international multicentre study combining data from multiple international trauma centres to collect adequate data.

Features of laparoscopic cholecystectomy in patients with chronic calculous cholecystitis and signs of ”non-functioning” gallbladder

Aim. To improve outcomes of laparoscopic cholecystectomy in patients with chronic cholecystitis and signs of “nonfunctioning” gallbladder via development of preventive, curative and diagnostic measures. Material and methods. Laparoscopic cholecystectomу was performed in 14 764 patients with chronic cholecystitis. Incidence and causes of intraoperative injury of extrahepatic bile ducts were retrospectively analyzed. Three basic forms of “non-functioning” gallbladder (hydropsy, sclerosis and atrophy, total filling by stones) were. Results. Biliary injury followed by bile leakage occurred in 38 (0.25%) cases. Intraoperative and early postoperative diagnosis was in 11 (28.9%) and 27 (71.1%) patients, respectively. Tangential trauma of common bile duct was found in 3 (7.8%) cases, complete intersection – in 8 (21%) patients. Herewith, 6 of them had sclerosis, 2 – total filling of gallbladder by stones. New diagnostic and curative approach was followed by only 2 (0.04%) cases of early postoperative bile leakage in 2010–2015. Injury of common bile duct was absent within the same period. Sclerosis and atrophy of gallbladder were diagnosed prior to surgery. Conclusion. There are 3 types of “non-functioning” gallbladder with risk of biliary trauma during laparoscopic cholecystectomy. Sclerosis and atrophy of gallbladder are predominantly followed by certain difficulties during laparoscopic cholecystectomy. New diagnostic and curative approach is useful to prevent iatrogenic biliary trauma.

Detection of traumatic pancreatic duct disruption in the modern era

BackgroundPancreatic trauma management hinges upon the presence or absence of pancreatic duct injury, but the optimal method of assessment is unclear. This study endeavored to evaluate the methods of pancreatic duct assessment in modern practice. MethodsPatients presenting to LAC + USC Medical Center (01/2008–06/2015) with a pancreatic injury were identified (ICD-9 codes). Demographics, clinical data, technique of duct evaluation, and outcomes were analyzed. Results71 patients with pancreatic injury were identified. 21 patients (30%) underwent CT scan (sensitivity 76%). Sixteen (76%) then underwent laparotomy while 5 (24%) were managed successfully nonoperatively. Most (n = 50, 70%) underwent immediate laparotomy. Overall, 66 patients (93%) were managed operatively. The majority were assessed intraoperatively for ductal injury with visual inspection alone (n = 62, 94%). Four (6%) underwent intraoperative pancreatography via duodenotomy/cholecystotomy, which were all inconclusive. ConclusionIn the evaluation of pancreatic duct injury, intraoperative pancreatography is frequently inconclusive and should have a limited role. Clinical suspicion for ductal injury based on intraoperative visual inspection alone should guide the management of pancreatic injuries.

Application of Delayed Surgical Managements in Patients with Stensen's Duct Injury

The study aimed to retrospectively evaluate surgical treatment outcomes after delayed parotid gland and duct injuries. Nine patients subjected to parotid gland and duct injuries with 1- to 3-month treatment delay were retrospectively evaluated with special reference of etiology, past medical history, and injury location. Conservative treatment, microsurgical anastomosis, and diversion of salivary flow or ligation were chosen for delayed parotid gland and duct injuries concerning to their site of injury, time of repair and procedures. Assistant treatment as pressure dressing was adopted thereafter. All patients experienced an uneventful recovery at the time of finalizing the study. Two patients received Stensen's duct ligation, 5 received microsurgical anastomosis and 2 accepted salivary flow diversion for 5 patients with sialoceles and 4 patients with fistulas, and no re-occurrence was found. Facial paralysis occurred after surgery in 4 patients, and 3 of them recovered after the nerve nutrition treatment. Our study suggested that appropriate surgical treatment is efficient for the re-establishment of the tissue function and facial aesthetic for delayed injury of the parotid and its duct.

SURGICAL TREATMENT OF IATROGENIC LESIONS OF THE BILIARY TRACT IN PATIENTS WITH CHRONIC OPISTHORCHOSIS

Aim. To determine incidence and causes of iatrogenic injuries of bile ducts during cholecystectomy in patients with chronic opisthorchosis and features of its surgical correction. Materials and Methods. The results of 7147 cholecystectomies were analyzed. General clinical and modern instrumental methods were used in survey. Statistical analysis was performed using software package Statgraphics 6.0 Plus for Windows. Results. Bile ducts injuries were observed in 41 (0.57%) patients with gallstone disease including 20 (1.13%) cases with concomitant chronic opisthorchosis and in 21 (0.36%) patients without opisthorchosis. Traditional and laparoscopic cholecystectomy was associated with bile ducts injuries in 0.65% and 0.43% of cases respectively. Large traumas were prevalent (61%) according to the McMachon classification (1995). Pathognomonic pathologic changes of the biliary system and infiltrative changes in the gall bladder neck were main reasons of ducts injuries in case of opisthorchosis and bladder, cholelithiasis, cholecystectomy, iatrogenic lesion, opisthorchosis, bile ducts, drainage, reconstructive surgical procedure. without it respectively. Recovery operations were performed in 55,8% of cases. Reconstructive interventions were performed in 23.3% of patients. Posttraumatic cicatrical strictures of ducts and biliodigestive anastomoses occured 2.6 times more frequent in patients with opisthorchosis. Postoperative mortality was 33.3%, in patients without opisthorchosis – 10.5% ( p < 0.05). Conclusion. Chronic opisthorchosis increases the frequency of duct injuries during cholecystectomy in 3.1 times. The disease complicates technique of recovery and reconstructive operations and increases postoperative mortality.

Genetic and pharmacologic abrogation of Snail1 inhibits acinar-to-ductal metaplasia in precursor lesions of pancreatic ductal adenocarcinoma and pancreatic injury.

Pancreatic cancer (PDAC) is one of the most dismal of human malignancies. Inhibiting or delaying the progression of precursor lesions of PDAC, pancreatic intraepthial neoplasia (PanINs), to invasive cancer, would be a major step. In the present study, we used a transgenic murine model of pancreatic cancer to evaluate the impact of a conditional knockout of the transcription factor Snail1, a major factor in epithelial-to-mesenchymal transition, on acinar-to-ductal formation and on PanIN progression. By interbreeding conditional LsL-Snail floxf/wt ; LsL-Kras G12D and Pdx1-Cre strains, we obtained LsL-Kras G12D ;Pdx1-Cre(KP) mice, Snail1 heterozygous knockout LsL-Kras G12D ; LsL-Snail flox/- ;Pdx1-Cre(KPShet) mice or Snail1 homozygous knockout LsL-Kras G12D ;LsL-Snail flox/flox ;Pdx1-Cre(KPS) mice. Mice were then followed in a longitudinal study for 2, 4, 6, 8, 10, and 12 months. Furthermore, in mice with a genetic or pharmacological inhibition of Snail1, using the Snail1 inhibitor GN25, a model of pancreatic injury by administration of cerulein was introduced to evaluate ADM formation in this setting. A translational approach with a tissue microarray (TMA) of human PanINs and an in vivo nude mouse platform to test GN25 in human pancreatic adenocarcinoma was then adopted. Quantification of PanINs showed delayed initiation and progression of PanIN lesions at all ages in both homozygous and heterozygous Snaildel1;Pdx-1-Cre;LSL-KrasG12D/+-Mice. PanINs at TMA revealed snail expression in the majority of cases. GN25 showed growth inhibition in 2/2 human pancreatic adenocarcinomas using a nude mice in vivo platform. Genetic and pharmacologic abrogation of Snail1 signaling in exocrine pancreas impairs development of acinar-to-ductal metaplasia following cerulein-mediated pancreatic injury. The present study suggests a fundamental new approach to delay the progression of PDAC.

Diminished Survival in Patients with Bile Leak and Ductal Injury: Management Strategy and Outcomes

The increased incidence of bile duct injuries (BDIs) after the adoption of laparoscopic cholecystectomy has been well documented. However, the longitudinal impact of bile leaks and BDIs on survival and healthcare use have not been studied adequately. The aims of this analysis were to determine the incidence, long-term outcomes, and costs of bile leaks and ductal injuries in a large population. The California Office of Statewide Health Planning and Development database was queried from 2005 to 2014. Bile leaks, BDIs, and their management strategy were defined. Survival was calculated by Kaplan-Meier failure estimates with multivariable regression and propensity analyses. Cost analyses used inflation adjustments and institution-specific cost-to-charge ratios. Of 711,454 cholecystecomies, bile leaks occurred in 3,551 patients (0.50%) and were managed almost exclusively by endoscopists. Bile duct injuries occurred in 1,584 patients (0.22%) with 84% managed surgically. Patients with a bile leak were more likely to die at 1 year (2.4% vs 1.4%; odds ratio 1.85; p < 0.001). Similarly, BDI patients had an increased 1-year mortality (7.2% vs 1.3%; odds ratio 2.04; p < 0.0001). Survival of BDI patients was better with an operative approach (odds ratio 0.19; p < 0.001) when compared with endoscopic management. Operatively managed BDIs were also associated with fewer emergency department visits and readmissions, as well as lower cumulative costs at 1 year ($60,539 vs $118,245; p < 0.001). The 0.22% incidence of BDIs observed in California is lower than reported in the first decade after the introduction of laparoscopic cholecystectomy. Bile leaks are 2.3 times more common than BDIs. Patients with a bile leak or BDI have diminished survival. Surgical repair of a BDI leads to enhanced survival and reduced cumulative cost compared with endoscopic management.

СОВРЕМЕННОЕ СОСТОЯНИЕ И ПЕРСПЕКТИВЫ ЛЕЧЕНИЯ СВИЩА ПОДЖЕЛУДОЧНОЙ ЖЕЛЕЗЫ

Цель. Оценка современных методов лечения свища поджелудочной железы (СПЖ) с рекомендациями их выбора на современном этапе.&#x0D; Материалы и методы. Проанализированы результаты лечение 21 больного по поводу СПЖ в возрасте от 28 до 70 лет. СПЖ с полным повреждением протока поджелудочной железы (ПЖ) сформировался у 11 больных, у 4 из них – после выполнения панкреатодуоденальной резекции. Неполное краевое повреждение отмечено у 10 больных, у 5 из них – после деструктивного острого панкреатита (ОП) с исходом в нагноившуюся кисту ПЖ. У 3 больных СПЖ образовался вследствие травмы живота, у 1 – после продольной панкреатоеюностомии по поводу хронического болевого панкреатита, у 1 – деструктивного ОП хвоста ПЖ. Длительность существования СПЖ от 2 мес до 1 года.&#x0D; Результаты. При выборе метода лечения использована разработанная нами классификация, основанная на анализе поражения протоковой системы ПЖ. Консервативное лечение проведено 8 больным, оперированы – 13, у 9 из них осуществлено внутреннее дренирование, в том числе у 2 – фистулоэнтеростомия по методике Альперовича, у 1 – продольная панкреатоеюностомия, у 1 – левосторонняя панкреатэктомия с иссечением свища. Все пациенты живы.&#x0D; Выводы.&#x0D; Улучшение результатов лечения СПЖ и профилактика их образования зависят от проведения патогенетически обоснованной консервативной терапии ОП, совершенствования техники хирургического вмешательства на ПЖ. По поводу наружного СПЖ с полным повреждением протока ПЖ показано оперативное вмешательство с адекватным курсом консервативной терапии. Хирургическое лечение должно быть индивидуальным, в условиях специализированного стационара.

Inhibition of Cdk5 Promotes β-Cell Differentiation From Ductal Progenitors.

Inhibition of notch signaling is known to induce differentiation of endocrine cells in zebrafish and mouse. After performing an unbiased in vivo screen of ∼2,200 small molecules in zebrafish, we identified an inhibitor of Cdk5 (roscovitine), which potentiated the formation of β-cells along the intrapancreatic duct during concurrent inhibition of notch signaling. We confirmed and characterized the effect with a more selective Cdk5 inhibitor, (R)-DRF053, which specifically increased the number of duct-derived β-cells without affecting their proliferation. By duct-specific overexpression of the endogenous Cdk5 inhibitors Cdk5rap1 or Cdkal1 (which previously have been linked to diabetes in genome-wide association studies), as well as deleting cdk5, we validated the role of chemical Cdk5 inhibition in β-cell differentiation by genetic means. Moreover, the cdk5 mutant zebrafish displayed an increased number of β-cells independently of inhibition of notch signaling, in both the basal state and during β-cell regeneration. Importantly, the effect of Cdk5 inhibition to promote β-cell formation was conserved in mouse embryonic pancreatic explants, adult mice with pancreatic ductal ligation injury, and human induced pluripotent stem (iPS) cells. Thus, we have revealed a previously unknown role of Cdk5 as an endogenous suppressor of β-cell differentiation and thereby further highlighted its importance in diabetes.