Extracorporeal Shock Wave Lithotripsy of Pancreatic Duct Stones

Chronic calcifying pancreatitis presents a major clinical problem, often requiring extensive surgery. Extracorporeal shock wave lithotripsy (ESWL) offers a new therapeutic option. We applied ESWL after endoscopic sphincterotomy of the pancreatic orifice in eight patients with impacted pancreatic duct stones. An electromagnetic lithotriptor (Siemens Lithostar, Erlangen, FRG) was used. Patients were treated in prone position under fluoroscopic control. A mean of 6,813 shock waves (range 1,500-10,000) was delivered in one or two sessions. Disintegration of stones was achieved in 6/8 patients, initial relief of pain in 7/8 patients, and total clearance of the pancreatic duct in 3/8 patients. One patient had an exacerbation of her pancreatitis one day after ESWL, which resolved rapidly with medical treatment. No other complications were observed. Four of five patients with fragmented stones had no abdominal complaints at follow-up (mean 17 months, range 3-27). Three patients in whom ESWL was not completely successful (two without and one with partial fragmentation) underwent an operation according to Puestow. Two of them still have abdominal complaints after surgery. From these data, we conclude that ESWL of pancreatic duct stones is a promising new alternative for surgery, when endoscopic stone extraction fails.     

Pancreatic Trauma in the Adult: Current Knowledge in Diagnosis and Management

Background/Aims: Although pancreatic trauma, isolated or not, is uncommon, it carries significant morbidity and mortality because of the delay in recognition and consequent treatment. Methods: The current knowledge of pancreatic injury, concerning the incidence, mechanism of induction, diagnosis, treatment, complications and outcome, is herein presented based on a literature review and our limited experience. Results: The diagnosis of pancreatic trauma entails a high index of suspicion because neither clinical nor laboratory evaluation provide pathognomonic elements. Patients with penetrating injuries are usually evaluated during laparotomy, while those with a blunt trauma can be managed conservatively, provided they are in a stable condition, there is no pancreatic duct involvement and care is intensive. At laparotomy, minor pancreatic injuries are best managed by drainage. Distal pancreatectomy is best suited for distal pancreatic trauma with ductal involvement. For severe trauma, Roux-en-Y pancreaticojejunostomy, pancreaticogastrostomy, duodenal diversion operations and Whipple’s procedure are all indicated according to the preoperative evaluation and intraoperative findings. Independent of the procedure to be performed, drainage is mandatory. Conclusion: Because pancreatic injury is rare, most general surgeons lack experience and ability to deal with such injured patients. Therefore, an experienced and skilled surgeon should govern the management of pancreatic trauma in order to minimize the incidence of morbidity and mortality.     

Expression of Heat Shock Protein 70 Modulates the Chemoresponsiveness of Pancreatic Cancer

Background/Aims

Heat shock protein (HSP) 70 is constitutively overexpressed in pancreatic cancer cells (PCCs) and appears to confer protection against chemotherapeutics. We investigated whether modulating HSP 70 increases chemoresponsiveness to gemcitabine in PCCs.

Methods

Varying concentrations of quercetin and gemcitabine, either alone or in combination, were added to PCCs (Panc-1 and MiaPaCa-2). MTT assay was performed to analyze cell viability. HSP 70 expression was assessed by Western blot analysis. Apoptosis was determined by measuring caspase-3 activity. Western blot for the LC3-II protein detected the presence of autophagy.

Results

HSP 70 levels were not affected by the incubation of Panc-1 and MiaPaCa-2 cells with gemcitabine, whereas with quercetin, the levels were reduced in both cell lines. The viability of both Panc-1 and MiaPaCa-2 cells significantly decreased with gemcitabine treatment but not with quercetin. A combination of gemcitabine and quercetin decreased the viability of both cell lines in a dose-dependent manner, which was more pronounced than gemcitabine treatment alone. Treatment with either gemcitabine or quercetin augmented caspase-3 activity in both cell lines, and a combination of these compounds further potentiated caspase-3 activity. LC3-II protein expression was negligible with gemcitabine treatment but marked with quercetin. The addition of gemcitabine to quercetin did not potentiate LC3-II protein expression.

Conclusions

Modulation of HSP 70 expression with quercetin enhanced the chemoresponsiveness of PCCs to gemcitabine. The mechanism of cell death was both apoptosis and autophagy.     

Trauma

Ohne Zusammenfassung     

Trauma

Ohne Zusammenfassung     

A Phase I Pilot Study of Autologous Heat Shock Protein Vaccine HSPPC-96 in Patients With Resected Pancreatic Adenocarcinoma

We performed a phase I pilot study to determine if autologous vaccine HSPPC-96 (gp96, Oncophage) could be purified from completely resected pancreas adenocarcinomas, to determine patient tolerance of vaccine and to explore immune responses and clinical outcomes of these patients. Subjects were vaccinated with 5 microg of autologous HSPPC-96 weekly for 4 doses. Serial ELISPOT assays of T cells for antitumor reactivity were performed. Subjects received neither adjuvant chemotherapy nor radiation. Ten patients received a full course of vaccinations. No dose-limiting toxicities were encountered. Immediate freezing in liquid nitrogen of the tumor specimen resulted in improved vaccine yield. Median overall survival is 2.2 years (Kaplan-Meier estimate). Autologous anti-HSPPC-96 ELISPOT reactivity increased significantly in 1 of 5 patients examined and a second had an increase of unclear significance. Three of 10 treated patients are alive without disease at 2.6, 2.7, and 5.0 years follow-up. There was no observed correlation between immune response and prognosis. This study demonstrates the feasibility of preparing HSPPC-96 from pancreatic adenocarcinomas. Examination of this novel approach using multiple dose levels is 1 approach to further investigate the immunogenicity and clinical utility of HSPPC-96 vaccination in this setting.     

Incidence and Significance of Biliary Stricture in Chronic Pancreatitis Patients Undergoing Extracorporeal Shock Wave Lithotripsy for Obstructing Pancreatic Duct Stones

Background/AimsThis study assessed the significance of biliary stricture in symptomatic chronic pancreatitis patients requiring extracorporeal shock wave lithotripsy (ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) to remove obstructing pancreatic calculi.MethodsA total of 97 patients underwent ESWL followed by ERCP to remove pancreatic calculi between October 2014 and October 2017 at Virginia Mason Medical Center. Significant biliary stricture (SBS) was defined as a stricture with upstream dilation on computed tomography scan or magnetic resonance cholangiopancreatography scans accompanied by cholestasis and/or cholangitis. SBS was initially managed by either a plastic stent or fully covered self-expandable metallic stent (fcSEMS). If the stricture did not resolve, the stent was replaced with either multiple plastic stents or another fcSEMS. Data were collected by retrospectively reviewing the medical records.ResultsBiliary strictures were noted in approximately one-third of patients (34/97, 35%) undergoing ESWL for pancreatic calculi. Approximately one-third of the biliary strictures (11/34, 32%) were SBS. Pseudocysts were more frequently found in those with SBS (36% vs 8%, p=0.02), and all pseudocysts in the SBS group were located in the pancreatic head. The initial stricture resolution rates with fcSEMSs and plastic prostheses were 75% and 29%, respectively. The overall success rate for stricture resolution was 73% (8/11), and the recurrence rate after initial stricture resolution was 25% (2/8).ConclusionsAlthough periductal fibrosis is the main mechanism underlying biliary stricture development in chronic pancreatitis, inflammation induced by obstructing pancreatic calculi, including pseudocysts, is an important contributing factor to SBS formation during the acute phase.     

Spinales Trauma

Zusammenfassung Spinale Traumen stellen mit etwa 55 000 stationären Behandlungsfällen pro Jahr in Deutschland ein relevantes Krankheitsbild dar. Von besonderer Bedeutung sind die Fälle mit Rückenmarkverletzung, die nach den Daten der Krankenhaus- Diagnosestatistik ca. 20% der stationären Aufenthalte ausmachen. Der Zusammenhang zwischen Wirbelsäulen- und Rückenmarkverletzung ist komplex, da sowohl Wirbelsäulenverletzung ohne Rückenmarkbeteiligung, Wirbelsäulenverletzungen mit Rückenmarkschädigung als auch Rückenmarkverletzungen ohne Wirbelsäulenbeteiligung vorkommen.Für die Verletzung der Wirbelsäule sprechen Schmerz und Fehlhaltung, für die Verletzung des Rückenmarks neurologische Ausfälle kaudal der Verletzungsstelle. Die Versorgung vor Ort umfasst als erstes die Sicherung der Vitalfunktionen. Hierbei und im Anschluss sollte zur Vermeidung zusätzlicher Schäden die Wirbelsäule immobilisiert werden. Nach der derzeitigen Datenlage ist die frühe, hochdosierte Methylprednisolon-Gabe zu empfehlen. Die Versorgung der Patienten sollte in einer Fachklinik erfolgen, die über die notwendigen diagnostischen und therapeutischen Möglichkeiten verfügt.Evidenz-basierte Daten zum Nutzen einer operativen versus konservativen Versorgung von Wirbelsäulenverletzungen gibt es bislang nicht. Für die Prognose von Rückenmarkverletzungen ist die Art des therapeutischen Vorgehens wohl ohne Belang. Der Vorteil der operativen Stabilisierung der Wirbelsäule besteht in einer Vermeidung von Sekundärkomplikationen und einer Frühmobilisierung/-rehabilitation des Patienten.Serie: Die Intensivtherapie bei Traumen des Nervensystems Herausgegeben von J. Meixsensberger (Leipzig) und Th. Steiner (Heidelberg)     

Pancreatic Carcinogenesis

Pancreatic cancer is an almost universally lethal disease. Research over the last two decades has shown that pancreatic cancer is fundamentally a genetic disease, caused by inherited germline and acquired somatic mutations in cancer-associated genes. Multiple alterations in genes that are important in pancreatic cancer progression have been identified, including tumor suppressor genes, oncogenes, and genome maintenance genes. Furthermore, the identification of non-invasive precursor lesions of pancreatic adenocarcinoma has led to the formulation of a multi-step progression model of pancreatic cancer and the subsequent identification of early and late genetic alterations culminating in invasive cancer. In addition, an increased understanding of the molecular basis of the disease has facilitated the identification of new drug targets enabling rational drug design. The elucidation of genetic alterations in combination with the development of high-throughput sensitive techniques should lead to the discovery of effective biomarkers for early detection of this malignancy. This review focuses mainly on the current knowledge about the molecular insights of the pathogenesis of pancreatic ductal adenocarcinoma.     

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胰性脑病(pancreatic encephalopathy,PE),指急性胰腺炎并发中枢神经系统的损害,是胰腺炎少见的严重并发症,常发生于急性胰腺炎的病程中,也可以发生在轻型胰腺炎或慢性胰腺炎的急性发作过程中。1923年Lowell首次在临床观察中发现,其定义于1941年由Rothemich提出,主要临床表现为定向力障碍、烦躁不安、妄想、幻觉、意识不清或反应迟钝、表情淡漠、抑郁等精神神经障碍,亦称酶性脑病。1发病机制目前对PE发病机制的研究虽然取得了一定的进展,但尚未完全清楚[1-3]。一般认为,与胰腺脂酶、磷脂酶A2、炎症介质及其它因素如低氧血症和急性呼吸窘…     

Pancreatic Ascites

A brief review of TPN might more clearly point out and explain some of the major areas of this protocol. The use of subclavian vein catheterization for hyperosmolar solutions is the key to TPN. The tip of the catheter resides in the superior vena cava, so solutions with a concentration of 1,500-2,200 mOsm/l. (over five times the osmolarity of serum) can be infused at a rate of 2-3 ml./min. while being diluted by a blood flow of 2-5 l./min. (a dilution factor of a thousand). The site of the catheter is in a large vein. The cutaneous entry site of the catheter is in the pectoral skin below the clavicle; site must be kept scrupulously clean and dressed sterilely. Because of potential complications, the patient should be carefully observed and monitored.