Long-term outcome after pancreatic stenting in severe chronic pancreatitis.

BACKGROUND AND STUDY AIMS: Although it has been proved that pancreatic stenting is effective in the symptomatic management of severe chronic pancreatitis, long-term outcomes after stent removal have not been fully evaluated. PATIENTS AND METHODS: A total of 100 patients (75 men, 25 women; median age 49) with severe chronic pancreatitis and pancreatic duct strictures were successfully treated for pancreatic pain using polyethylene pancreatic stents and were followed up for at least 1 year after stent removal. The stents were exchanged "on demand" (in cases of recurrence of pain) and a definitive stent removal was attempted on the basis of clinical and endoscopic findings. Clinical variables were retrospectively assessed as potential predictors of re-stenting. RESULTS: The etiology of the chronic pancreatitis was alcoholic (77 %), idiopathic (18 %), or hereditary (5 %). Patients were followed up for a median period of 69 months (range 14 - 163 months) after study entry, including a median period of 27 months (range 12 - 126 months) after stent removal. The median duration of pancreatic stenting before stent removal was 23 months (range 2 - 134 months). After attempted definitive stent removal, 30 patients (30 %) required re-stenting within the first year of follow-up, at a median time of 5.5 months after stent removal (range 1 - 12 months), while in 70 patients (70 %) pain control remained adequate during that period. By the end of the follow-up period a total of 38 patients had required re-stenting and four ultimately underwent pancreaticojejunostomy. Pancreas divisum was the only factor significantly associated with a higher risk of re-stenting (P = 0.002). CONCLUSIONS: The majority (70 %) of patients with severe chronic pancreatitis who respond to pancreatic stenting maintain this response after definitive stent removal. However, a significantly higher re-stenting rate was observed in patients with chronic pancreatitis and pancreas divisum.

Tratamiento del dolor en pancreatitis crónica calcificante con endoscopía y ondas de choque extracorpóreas. A propósito de un caso / Treatment of pain in chronic calcification pancreatitis with endoscopy and extracorporeal shock wave lithotripsy. Presentation of a case

Abdominal pain is the most frequent symptom of chronic pancreatitis and may, on occasions, lead to great treatment problems. The case of a 56-years-old patient with idiopathic chronic pancreatitis calcifying who showed intracanalicular lithiasis is reported. Treatment with endoscopy and extracorporal shock wave lithotripsy (ESWL) was successful.

Tratamiento del dolor en pancreatitis crónica calcificante con endoscopía y ondas de choque extracorpóreas. A propósito de un caso / Treatment of pain in chronic calcification pancreatitis with endoscopy and extracorporeal shock wave lithotripsy. Presentation of a case

Abdominal pain is the most frequent symptom of chronic pancreatitis and may, on occasions, lead to great treatment problems. The case of a 56-years-old patient with idiopathic chronic pancreatitis calcifying who showed intracanalicular lithiasis is reported. Treatment with endoscopy and extracorporal shock wave lithotripsy (ESWL) was successful. (Au)

[Treatment of pain in chronic calcifying pancreatitis with endoscopy and extracorporeal shock wave lithotripsy. A case report]. / Tratamiento del dolor en pancreatitis crónica calcificante con endoscopía y ondas de choque extracorpóreas. A propósito de un caso.

Abdominal pain is the most frequent symptom of chronic pancreatitis and may, on occasions, lead to great treatment problems. The case of a 56-years-old patient with idiopathic chronic pancreatitis calcifying who showed intracanalicular lithiasis is reported. Treatment with endoscopy and extracorporal shock wave lithotripsy (ESWL) was successful.

Tratamiento del dolor en pancreatitis crónica calcificante con endoscopía y ondas de choque extracorpóreas. A propósito de un caso. / [Treatment of pain in chronic calcifying pancreatitis with endoscopy and extracorporeal shock wave lithotripsy. A case report]

Abdominal pain is the most frequent symptom of chronic pancreatitis and may, on occasions, lead to great treatment problems. The case of a 56-years-old patient with idiopathic chronic pancreatitis calcifying who showed intracanalicular lithiasis is reported. Treatment with endoscopy and extracorporal shock wave lithotripsy (ESWL) was successful.

Endoscopic pancreatic drainage in chronic pancreatitis associated with ductal stones: long-term results.

BACKGROUND: In severe chronic pancreatitis associated with intraductal stones, therapeutic endoscopy aims to reduce increased intraductal pressure by pancreatic sphincterotomy and stone clearance. METHODS: Results of treatment were evaluated in 70 new patients who underwent pancreatic sphincterotomy and attempted stone removal. Technical results and frequency of pain relief and recurrence are compared. RESULTS: Complete ductal clearance of calculi was obtained in 50% of cases. Immediate clinical improvement occurred in 95% of patients with painful attacks. No severe complications or mortality occurred. Fifty-four percent of all patients with painful chronic pancreatitis did not experience any pain recurrence within 2 years. Associations found to be statistically significant by multivariate analysis were ductal clearance and extracorporeal shock wave lithotripsy, pain disappearance and ductal clearance, pain recurrence and long evolution, and severe disease before treatment and presence of a ductal substenosis. CONCLUSIONS: In this subset of patients our results indicate that the pain of chronic pancreatitis is mainly related to increased intraductal pressure. Endoscopic management appears to be a safe, conservative, alternative to surgery. The best results are obtained when it is performed early in the course of calcifying chronic pancreatitis.

Management of common bile duct stricture caused by chronic pancreatitis with metal mesh self expandable stents.

Twenty patients with chronic pancreatitis and signs of biliary obstruction were treated by endoscopic placement of self expandable metal mesh stents, and followed up prospectively. Eleven had been treated previously with plastic endoprostheses. All had persistent cholestasis, seven patients had jaundice, and three overt cholangitis. Endoscopic stent placement was successful in all cases. No early clinical complication was seen and cholestasis, jaundice or cholangitis rapidly resolved in all patients. Mean follow up was 33 months (range 24 to 42) and consisted of clinical evaluation, ultrasonography, and endoscopic retrograde cholangiopancreatography (ERCP). In 18 patients, successive ERCPs and cholangioscopies have shown that the metal mesh initially embeds in the bile duct wall and is rapidly covered by a continuous tissue by three months. The stent lumen remained patent and functional throughout the follow up period except in two patients who developed epithelial hyperplasia within the stent resulting in recurrent biliary obstruction, three and six months after placement. They were treated endoscopically with standard plastic stents with one of these patients ultimately requiring surgical drainage. No patient free of clinical or radiological signs of epithelial hyperplasia after six months developed obstruction later. This new treatment could become an effective alternative to surgical biliary diversion if further controlled follow up studies confirm the initial impression that self expandable metal mesh stents offer a low morbidity alternative for longterm biliary drainage in chronic pancreatitis without the inconvenience associated with plastic stents.

Endoscopic management of chronic pancreatitis.

The indications of endoscopic management for chronic pancreatitis are strictly related to the classification of severe types and to the particular anatomy of the ducts: 1. Impacted or distal calculi: endoscopic pancreatic sphincterotomy (EPS) alone followed by ESWL when extraction fails. 2. Stone(s) and stricture: EPS, ESWL, NPC, and then 10F plastic stenting. 3. Relapsing strictures (with upwards dilatation) after 6 to 12 months stenting: silicone covered self expanding stent in a trial, versus surgical pancreaticojejunostomy. 4. Paraduodenal cyst bulging into the duodenum: ECD. 5. Jaundice and/or cholestasis due to stricture of the intrapancreatic CBD: 10F single or multiple plastic stent for calibration during 3 months. For relapsing cholestasis and stricture, 30F metal mesh stent versus surgical hepaticojejunostomy. The indications of endoscopic management for chronic pancreatitis are specific and require complete imaging and functional check up (ERCP, CT scanner, endosonography, pancreatic function tests). The technique is quite difficult and requires definition fluoroscopy, appropriate devices and experienced team. On this condition, the complication rate is very low and usually medically controlled. Treatment does not compromise any further surgery. Endoscopy allows to avoid or to postpone surgery which indication will become better defined and selected in the future.

Endoscopic varix ligation: a promising new technique?

Endoscopic varix ligation is a new promising endoscopic method which compete with endoscopic sclerotherapy both during acute bleeding and the chronic setting where the aim is to obliterate varices as soon as possible with minimal side effects.

Factors related to early mortality in cirrhotic patients bleeding from varices and treated by urgent sclerotherapy.

Variceal haemorrhage in cirrhotic patients carries a high early mortality even when balloon tamponade or emergency sclerotherapy are applied. The aim of this study to identify patients dying within six weeks of their first variceal haemorrhage. One hundred and twenty one patients with parenchymal cirrhosis presenting with the first variceal bleeding episode between June 1983 and December 1988 were studied. Nineteen patients were excluded for various reasons. Emergency sclerotherapy was carried out in cases of active bleeding or where there were endoscopic signs of recent bleeding, and then regularly repeated afterwards. Of the 24 variables studied and included in a multivariate analysis using a logistic regression model, three had an independent prognostic value: encephalopathy, prothrombin time, and the number of blood units transfused within the 72 hours of time zero. The subsequent regression equation was able to predict 89% of the patients who will die and 97% of the patients who will still be alive six weeks after their first variceal haemorrhage treated by sclerotherapy. Pugh score was less discriminatory than these last three variables in terms of accuracy of adjustment, goodness of fit to the model, receiver operating characteristic curves, and percentage correct prediction. To measure the accuracy of the prediction rule, our model was applied to another series of 28 cirrhotic patients admitted with their first variceal bleeding during the next period (January 1989 to May 1990). Death and survival were correctly predicted in respectively 82% and 94% of the cases. The use of this score is recommended for the selection of patients with high early mortality after variceal bleeding despite sclerotherapy, and for the design of new therapeutic trials.

Endoscopic treatment of esophagogastric varices.

We report our current management of variceal bleeding with endoscopic sclerotherapy. We emphasize the importance of resuscitation and of recording at time zero and within the first 72 hours clinical and laboratory indicators, as these influence the management of these patients. Primary sclerotherapy using Histoacryl for active bleeding and Ethoxysclerol for recent bleeding should be performed as soon as the patient is stable hemodynamically. As we have identified factors related to the severity of hemorrhage and of liver failure degree which can predict early failure of sclerotherapy, patients presenting with these findings should be, in the future, referred quickly toward alternative therapies among which non-surgical intrahepatic shunt appears a promising modality.

Treatment of peptic ulcer severe bleeding.

The success of a defined management policy op peptic ulcer haemorrhage which incorporates endoscopic therapeutic intervention depends on the early identification of a high risk group of patients and a high risk group of ulcers. The high risk group of patients consists of those likely to experience further bleeding on the basis of clinical prognostic indicators: shock and severe anaemia on admission and the pattern of bleeding; or tolerate rebleeding and emergency surgery poorly: patients over 60 years and those with associated disease. UGI endoscopy should be performed early (within 6-12 hours) in this group in order to identify the bleeding point and provide prognostic information regarding the risk of further haemorrhage. Peptic ulcers with major stigmata of recent bleeding (spurting or non-bleeding visible vessel) have high risk of rebleeding, the risk is even greater when major stigmata of recent haemorrhage (SRH) are associated with shock on admission. Patients with such ulcers should be monitored intensively and receive endoscopic haemostatic treatment in order to terminate active haemorrhage or prevent rebleeding thereby avoiding the need for emergency surgery with its attendant morbidity and mortality. Patients with ulcers with minor or no SRH have a very low risk of rebleeding and don't require intensive monitoring or endoscopic treatment and can be discharged from hospital early. Ulcers which cannot be completely characterized have an intermediate risk of rebleeding and should be managed as high risk lesions. Secondary to the anatomy of the visible vessel any haemostatic endoscopic treatment should be applied around, but avoiding, the sentinel clot. Well-designed randomized controlled trials of endoscopic haemostatic treatment of peptic ulcer haemorrhage in which stratification of risk was based on the SRH, have demonstrated for non-bleeding vessel a significant reduction in rebleeding and in emergency surgery, for spurting bleeding benefit was found only for the rebleeding risk. No advantage was demonstrated in each group of patients in term of mortality. Such studies also demonstrate the superiority of the Nd:YAG laser over the Argon laser. Perforation is a rare complication of Nd:YAG laser photocoagulation (less than 1%). Precipitation or aggravation of arterial haemorrhage during treatment of a visible vessel, as a result of a direct hit, is a more frequent complication (0-29%). Further laser treatment is successful in terminating 75% of these induced bleeds, the remainder requiring surgery. Preinjection of the ulcer with adrenaline does not appear to prevent this complication.(ABSTRACT TRUNCATED AT 400 WORDS)

Endoscopic stenting for biliary strictures.

A consensus is growing among units that have an experience in both endoscopic and percutaneous stenting techniques that the endoscopic approach of malignant biliary strictures is more comfortable for the patient and provides less complications. This article describes endoscopic biliary drainage in different malignant stenosis of the bile ducts and delineates the respective indications of percutaneous and endoscopic techniques together with the possible combination of these two methods in selected cases. It also tackles the question of the medical surgical approach of the patients, which might, thanks to a better selection, reduce the morbidity and mortality associated with surgery. The indications of biliary stenting in benign strictures, namely post operative or chronic pancreatitis associated biliary stenoses, are also discussed. Recently, new materials became available for endoscopic and percutaneous biliary drainage, and particularly metallic self expanding stents which might provide a better palliation among these patients. If these stents fulfill their promise on longer follow-up, they may replace the conventional stenting devices.

The switch of tau protein to an Alzheimer-like state includes the phosphorylation of two serine-proline motifs upstream of the microtubule binding region.

The paired helical filaments (PHFs) of Alzheimer's disease consist mainly of the microtubule-associated protein tau. PHF tau differs from normal human brain tau in that it has a higher Mr and a special state of phosphorylation. However, the protein kinase(s) involved, the phosphorylation sites on tau and the resulting conformational changes are only poorly understood. Here we show that a new monoclonal antibody, AT8, records the PHF-like state of tau in vitro, and we describe a kinase activity that turns normal tau into a PHF-like state. The epitope of AT8 is around residue 200, outside the region of internal repeats and requires the phosphorylation of serines 199 and/or 202. Both of these are followed by a proline, suggesting that the kinase activity belongs to the family of proline-directed kinases. The epitope of AT8 is nearly coincident with that of another phosphorylation-dependent antibody, TAU1 [Binder, L.I., Frankfurter, A. and Rebhun, L. (1985) J. Cell Biol., 101, 1371-1378], but the two are complementary since TAU1 requires a dephosphorylated epitope.

Stenting in severe chronic pancreatitis: results of medium-term follow-up in seventy-six patients.

Between January 1985 and September 1989, 75 patients presenting with severe chronic pancreatitis with distal stricture and upstream dilatation underwent stenting of the main pancreatic duct (MPD) through the major papilla (n = 54) or minor papilla (n = 21) in order to drain the predominant duct through a 10F plastic prosthesis. All patients had undergone biliary and pancreatic sphincterotomy with a few cases of complications, and the majority (84%) also ESWL in the period from October 1987 onwards without complications. Relief of pain (94%) occurred parallel to a decrease in the MPD diameter. In a mean follow-up period of 37 months improvement of the nutrition status and relief of pain was seen. Clogging of these large plastic stents was treated by replacement or by another endoscopic or surgical procedure. Complications were treated endoscopically. Further measures necessary due to failure of stenting consisted of laterolateral pancreatico-jejunostomy in 15% of patients and placement of self-expanding 18F metal mesh stents in 29%. There was no mortality due to surgery. It is concluded that stenting of distal strictures in the MPD can lead to rapid resolution of pancreatic pain due to ductal hypertension and is the best means for determining the cause of pain, providing an alternative to surgery. Significant improvement of a stricture by prolonged stenting is however unusual, and such patients treated endoscopically require close follow-up with stent replacement approximately once a year.

Extracorporeal shock-wave lithotripsy of pancreatic calculi.

Extracorporeal shock-wave lithotripsy (ESWL) has been used to disintegrate pancreatic stones located in the main pancreatic duct for 123 patients with severe chronic pancreatitis. Endoscopic management following ESWL is aimed at restoring the pancreatic flow to the duodenum. Stone disintegration was achieved in 122 patients, whereas a decrease in the main pancreatic duct diameter resulted in 111, and complete clearance of the main pancreatic duct was obtained in 72. Pain relief, complete (40/88) or partial (35/88), correlated significantly with the results of the endoscopic drainage of the main pancreatic duct (e.g., decrease in main pancreatic duct diameter). Relapsing pain was most often related to recurrent pancreatic duct obstruction. Of 76 patients whose body weight had decreased before ESWL, 54 gained weight. Improvement of the exocrine function, evaluated by the [14C]triolein breath test before and 11 months, on the average, after ESWL, was observed in 12 patients among 22 for whom this test was performed before and after treatment. Improvement of the endocrine function after relief of obstruction of the main pancreatic duct was less frequently recorded (4/41). ESWL of pancreatic stones is a new, safe, and highly effective method of facilitating the endoscopic procedures for relief of pancreatic duct obstruction in severe chronic pancreatitis.

Stenting in severe chronic pancreatitis: results of medium-term follow-up in seventy-six patients.

Between January 1985 and September 1989, 75 patients presenting with severe chronic pancreatitis with distal stricture and upstream dilatation underwent stenting of the main pancreatic duct (MPD) through the major papilla (n = 54) or minor papilla (n = 21) in order to drain the predominant duct through a 10 F plastic prosthesis. All patients had undergone biliary and pancreatic sphincterotomy with a few cases of complications, and the majority (84%) also ESWL in the period from October 1987 onwards without complications. Relief of pain (94%) occurred parallel to a decrease in the MPD diameter. In a mean follow-up period of 37 months improvement of the nutrition status and relief of pain was seen. Clogging of these large plastic stents was treated by replacement or by another endoscopic or surgical procedure. Complications were treated endoscopically. Further measures necessary due to failure of stenting consisted of laterolateral pancreatico-jejunostomy in 15% of patients and placement of self-expanding 18 F metal mesh stents in 29%. There was no mortality due to surgery. It is concluded that stenting of distal strictures in the MPD can lead to rapid resolution of pancreatic pain due to ductal hypertension and is the best means for determining the cause of pain, providing an alternative to surgery. Significant improvement of a stricture by prolonged stenting is however unusual, and such patients treated endoscopically require close follow-up with stent replacement approximately once a year.

Non-surgical management of severe chronic pancreatitis.

The observation that drainage of the MPD in selected cases of severe chronic pancreatitis has a radical benefit on pain reduction supports the hypothesis that pain is mainly due to obstruction of the MPD. Further follow-up study is needed to assess whether endoscopic management can prevent progression of the disease and especially postpone the onset of diabetes and steatorrhea. The iterative character of the endoscopic management is at least an advantage when compared with surgery, which, in principle, might be considered definitive in only one operation. The present excellent results of non-surgical management of chronic pancreatitis suggest that these new procedures will find a prominent role similar to that already achieved for biliary tract procedures. Therapeutic endoscopy of the pancreas and chronic pancreatitis has focused on the 'stone and stricture' nature of the disease, and techniques have developed accordingly.