Efficacy of lanreotide 30 mg on prevention of pain relapse after oral refeeding in patients with necrotizing acute pancreatitis. A phase II prospective multicentre study.

BACKGROUND: Pain relapse after oral refeeding occurs in 21% of the patients with acute pancreatitis, and in 35% of those with CT Balthazar's score > or =D [Gut 1997;40:262]. Somatostatin analogues may decrease the pain relapse rate by inhibiting exocrine pancreatic secretion. AIMS, PATIENTS AND METHODS: To assess the frequency of pain relapse in patients with acute necrotizing pancreatitis after treatment with one intramuscular injection of lanreotide 30 mg on the day before refeeding. The refeeding procedure was standardized and progressive. RESULTS: 23 patients were included in 4 centres. Acute pancreatitis was alcoholic (n = 11), biliary (n = 7), other (n = 5). Twelve patients had > or =3 Ranson's criteria. Balthazar's score (1985) was D or E in 7 and 16 patients, respectively. Median duration of pain and of interruption of oral feeding were 11 (3-23) and 16 (5-34) days, respectively. Median hospital stay was 22 (9-41) days. Only 1 patient (4.3 %) had pain occurring 3 days after refeeding. CONCLUSION: Pain relapse occurred in 4.3% of patients pretreated with the somatostatin analogue lanreotide, and this figure is lower than the expected 35% rate which was previously reported without preventive treatment. This suggests that one intramuscular injection of lanreotide 30 mg on the day before refeeding could decrease pain relapse in patients with acute necrotizing pancreatitis, but has to be confirmed in a phase III study.     

Successful treatment of benign biliary stricture by a covered self-expandable metallic stent in a patient with chronic pancreatitis

The patient was a 73 year old man for whom surgery under general anesthesia was difficult to perform because of pulmonary emphysema. In April 2003, he visited our hospital complaining of epigastralgia and dorsal pain, and was admitted under a diagnosis of acute exacerbation of chronic pancreatitis. In 2005, acute cholangitis concomitantly developed with acute exacerbation of chronic pancreatitis, for which a plastic stent was placed in the common bile duct. Cholangitis repeatedly developed every 2-3 months thereafter, and admission was required each time to exchange the stent. Surgery was considered but not applicable because of his poor respiratory function, and a partially covered self-expandable metallic stent was inevitably placed in the bile duct. Ten months later, an aberration of the metallic stent in the bile duct occurred, but it was dealt with by placing an additional metallic stent, and no cholangitis or pancreatitis developed until the patient died of respiratory insufficiency 3 years later. Placement of a covered self-expandable metallic stent might be an option for the treatment of benign biliary stricture, especially in patients at high risk from surgery.     

Should anticoagulants be administered for portal vein thrombosis associated with acute pancreatitis?

Venous complications in patients with acute pancreatitis typically occur as a form of splenic, portal, or superior mesenteric vein thrombosis and have been detected more frequently in recent reports. Although a well-organized protocol for the treatment of venous thrombosis has not been established, anticoagulation therapy is commonly recommended. A 73-year-old man was diagnosed with acute progressive portal vein thrombosis associated with acute pancreatitis. After one month of anticoagulation therapy, the patient developed severe hematemesis. With endoscopy and an abdominal computed tomography scan, hemorrhages in the pancreatic pseudocyst, which was ruptured into the duodenal bulb, were confirmed. After conservative treatment, the patient was stabilized. While the rupture of a pseudocyst into the surrounding viscera is a well-known phenomenon, spontaneous rupture into the duodenum is rare. Moreover, no reports of upper gastrointestinal bleeding caused by pseudocyst rupture in patients under anticoagulation therapy for venous thrombosis associated with acute pancreatitis have been published. Herein, we report a unique case of massive upper gastrointestinal bleeding due to pancreatic pseudocyst rupture into the duodenum, which developed during anticoagulation therapy for portal vein thrombosis associated with acute pancreatitis.     

Acute pancreatitis associated with high-concentration lipid emulsion during total parenteral nutrition therapy for Crohn's disease

A 17-yr-old boy with Crohn's disease and growth retardation developed an acute abdominal crisis while receiving total parenteral nutritional support. Acute pancreatitis was confirmed surgically. After recovery, in an attempt to provide adequate calories and to elucidate the inciting agent, he was rechallenged with his original total parenteral nutritional solution which contained 500 ml/day of a 20% fat emulsion. Symptoms and signs of acute pancreatitis quickly returned. Total parenteral nutrition was continued without the fat emulsion and symptoms and signs disappeared. This case suggests that acute pancreatitis was due to intolerance of high-concentration lipid emulsion.     

Pancreatitis associated with pleural-mediastinal pseudocyst, panniculitis and polyarthritis

We describe two patients with pancreatitis. One patient had acute pancreatitis of biliary origin and presented with small joint polyarthritis and panniculitis lesions. The other patient was originally hospitalised for dyspnoea with bilateral pleural effusion, and subsequently developed migratory polyarthritis. During his hospital stay he developed panniculitis lesions and a monoclonal IgG disorder of unknown significance. Very few patients with pancreatitis develop polyarthritis and panniculitis. The appearance of pseudocysts in the pleural and mediastinal cavity in the course of pancreatitis is an infrequent complication.     

SUCCESSFUL MANAGEMENT OF METASTASIS‐INDUCED PANCREATITIS BY ENDOSCOPIC PANCREATIC DUCT STENTING IN A CASE OF LARGE CELL LUNG CANCER

The prognosis for patients with metastasis‐induced acute pancreatitis (MIAP) is extremely poor. Although chemotherapy has been shown to improve overall survival in patients with MIAP, as well as in patients with small cell lung cancer, it is poorly tolerated by patients with severe pancreatitis. Furthermore, patients with a history of chemotherapy often develop multidrug‐resistant tumors. Here we report a first case of MIAP that was successfully managed by endoscopic pancreatic duct stenting. A 54‐year‐old man with pancreatic metastasis from large cell lung cancer developed acute pancreatitis approximately three times per month, despite a continuous conventional therapy for pancreatitis. As his disease was refractory to chemotherapy, he underwent endoscopic pancreatic duct stenting. The procedure was successful in controlling his pancreatitis, and he survived 7 months after the onset of a first acute pancreatitis. Our experience with this case suggests pancreatic duct stenting as one therapeutic method for MIAP.     

Effective infliximab treatment for a recurrent type of acute intestinal graft-versus-host disease accompanied by steroid-induced depression

A 22-year-old man with chronic active Epstein-Barr virus infection underwent allogeneic bone marrow transplantation (allo-BMT) from an HLA two allele-mismatched unrelated donor. Ten months after allo-BMT, he developed protein-losing enteropathy following a respiratory syncytial virus infection. A diagnosis of a recurrent type of acute graft-versus-host disease (GVHD) was made based on the histopathological findings, such as the infiltration of T lymphocytes into the superficial epithelium and crypts, and apoptotic bodies in crypts. Although methylprednisolone (mPSL: 10 mg/kg) administration for two consecutive days improved gastrointestinal symptoms, acute pancreatitis and severe depression developed in association with corticosteroid treatment. Reduction of mPSL and administration of infliximab (5 mg/kg/dose, 3 times) resulted in rapid improvement of depression and pancreatitis without aggravating intestinal GVHD. Recent studies have demonstrated that tumor-necrosis-factor (TNF)-α is associated with not only GVHD but also depression and acute pancreatitis. In the present case, anti-TNF-α treatment enabled us to reduce corticosteroid dose without aggravating GVHD, which suggests that this approach might be effective for the treatment of depression and acute pancreatitis.     

Case report: acute pancreatitis induced by Clozapine

Two percent of acute pancreatitis are drug induced. In the present paper, we reported the case of a 39 year-old patient with chronic-hallucinatory schizophrenia who developed symptomatic pancreatitis during the clozapine dose titration performed to reach the therapeutic range. Diagnosis of pancreatitis was suggested by clinical examination and abnormal laboratory values of pancreatic enzymes and confirmed by C-T scan and ultrasonography. The causal incrimination of clozapine in this case seems likely as all other possible causes of pancreatitis were excluded, as AP developed shortly after the introduction of the drug and as the pancreatic enzymes normalized after clozapine was stopped. No rechallenge to confirm the causal relationship was however attempted. So far, only eight cases of acute pancreatitis have been reported in association with clozapine use. Clozapine is an atypical antipsychotic drug which belongs to the chemical class of dibenzodiazepines. The mechanism by which clozapine could produce acute pancreatitis remained unclear. Nevertheless, we advocate a careful biological follow-up (measuring periodically the concentrations of amylase, lipase and triglycerides) during the treatment by clozapine.     

Acute pancreatitis induced by fluvastatin therapy

A 36-year-old male patient, after 3 months' treatment with fluvastatin 40 mg/d for hypercholesterolemia, presented with acute pancreatitis. The pancreatitis was mild, and the patient settled on medical treatment. Other causes of the disease were ruled out. Some months later, the patient reintroduced fluvastatin on his own initiative, which caused a recurrence of pancreatitis within a few days. Previous reports are reviewed, showing that statin-induced acute pancreatitis may occur within the first day of therapy or after several months. It is generally mild and runs a benign course, and no mortality has been reported. The frequency of this side effect is unknown, but it is most likely rare.     

Assessment of severity of acute pancreatitis according to new prognostic factors and CT grading

The assessment of severity at the initial medical examination plays an important role in introducing adequate early treatment and the transfer of patients to a medical facility that can cope with severe acute pancreatitis. Under these circumstances, “criteria for severity assessment” have been prepared in various countries, including Japan, and these criteria are now being evaluated. The criteria for severity assessment of acute pancreatitis in Japan were determined in 1990 (of which a partial revision was made in 1999). In 2008, an overall revision was made and the new Japanese criteria for severity assessment of acute pancreatitis were prepared. In the new criteria for severity assessment, the diagnosis of severe acute pancreatitis can be made according to 9 prognostic factors and/or the computed tomography (CT) grades based on contrast-enhanced CT. Patients with severe acute pancreatitis are expected to be transferred to a specialist medical center or to an intensive care unit to receive adequate treatment there. In Japan, severe acute pancreatitis is recognized as being a specified intractable disease on the basis of these criteria, so medical expenses associated with severe acute pancreatitis are covered by Government payment.     

Lanreotide Autogel® for Acromegaly

Since their introduction into clinical practice, somatostatin analogs have been the pharmacological therapy of choice for the treatment of acromegaly. The first preparations of somatostatin analogs available for clinical use were administered subcutaneously two or three times daily, which was not optimal with respect to patient compliance. The introduction of long-acting formulations of somatostatin analogs has overcome this inconvenience. Lanreotide Autogel, a new viscous, supersaturated, aqueous solution of lanreotide, is available in a prefilled syringe and administered by deep subcutaneous injection every 28 days. Lanreotide Autogel has different pharmacokinetic properties from the earlier lanreotide slow-release (SR) formulation, which may account for its better tolerability. Furthermore, lanreotide Autogel is at least as efficacious as the other somatostatin analogs in lowering growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in the majority and in restoring safe GH and age-normalized IGF-1 levels in about 50-60% of patients with acromegaly. In conclusion, lanreotide Autogel is a valuable new addition to the acromegaly treatment armamentarium. Patients receiving intramuscular lanreotide SR injections every 7-14 days can be switched to an appropriate dose of deep subcutaneous lanreotide Autogel every 28 days, without any impact on safety or loss of efficacy.     

Markers for predicting severity and progression of acute pancreatitis

Several tools have been developed for severity stratification in acute pancreatitis. They include single biochemical markers, imaging methods, and complex scoring systems, all of which aim at an early detection of severe acute pancreatitis to optimise monitoring and treatment of patients as early as possible. Among single biochemical markers, C-reactive protein (CRP) remains the most useful. Despite its delayed increase, peaking not earlier than 72 h after the onset of symptoms, it is accurate and widely available. Many other markers have been evaluated for their usefulness, and for some of them very promising data could be shown. Among them interleukin 6 seems to be the most promising parameter for use in clinical routine. For the detection of pancreatic infection, procalcitonin is the most sensitive, and can be used as an indicator for the need for fine-needle aspiration of pancreatic necrosis. Regarding imaging, contrast-enhanced computed tomography is still the reference method for the detection of necrotising acute pancreatitis. Pancreatitis-specific scoring systems have been shown to be of value for the prediction of severity and progression of acute pancreatitis, but cannot be applied any earlier than 48 h after admission to hospital. The APACHE-II score has not been developed specifically for acute pancreatitis and is rather complex to assess, but has been proven to be an early and reliable tool. Indication, timing and consequences of the methods applied need to be carefully considered and incorporated into clinical assessments to avoid costs and harm to the patient.     

Acute pancreatitis： Etiology and common pathogenesis

Acute pancreatitis is an inflammatory disease of the pancreas. The etiology and pathogenesis of acute pancreatitis have been intensively investigated for centuries worldwide. Many causes of acute pancreatitis have been discovered, but the pathogenetic theories are controversial. The most common cause of acute pancreatitis is gallstone impacting the distal common bile-pancreatic duct. The majority of investigators accept that the main factors for acute billiary pancreatitis are pancreatic hyperstimulation and bile-pancreatic duct obstruction which increase pancreatic duct pressure and active trypsin reflux.Acute pancreatitis occurs when intracellular protective mechanisms to prevent trypsinogen activation or reduce trypsin activity are overwhelmed. However, little is known about the other acute pancreatitis. We hypothesize that acute biliary pancreatitis and other causes of acute pancreatitis possess a common pathogenesis. Pancreatic hyperstimulation and pancreatic duct obstruction increase pancreatic duct pressure, active trypsin reflux, and subsequent unregulated activation of trypsin within pancreatic acinar cells. Enzyme activation within the pancreas leads to auto-digestion of the gland and local inflammation. Once the hypothesis is confirmed, traditional therapeutic strategies against acute pancreatitis may be improved. Decompression of pancreatic duct pressure should be advocated in the treatment of acute pancreatitits which may greatly improve its outcome.     

Recurrent pancreatitis after trimethoprim-sulfamethoxazole rechallenge

We report a female patient who repeatedly developed pancreatitis after trimethoprim-sulfamethoxazole (TMP/SMX) use. During childhood she had undergone an ureterosigmoidostomy after which she had been on TMP/SMX 480 mg daily as prophylaxis for pyelonephritis for many years. The patient presented with abdominal pain caused by acute pancreatitis. No other cause, except for TMP/SMX use, could be identified. A causal relationship was confirmed by relapse of the pancreatitis after rechallenge. Our case is unique in demonstrating that acute pancreatitis related to the use of TMP/SMX may occur even after long-term treatment. We advise that the medication is discontinued immediately if a causal relationship with pancreatitis is suspected.     

The first histological demonstration of pancreatic oxidative stress in human acute pancreatitis.

Necrotizing acute pancreatitis is associated with an inflammatory explosion involving numerous pro-inflammatory mediator cascades and oxidative stress. Acinar oxygen free radical production aggravates pancreatic tissue damage, and promotes cellular adhesion molecule upregulation resulting in leukocyte adherence and activation. The cerium capture oxygen free radical histochemistry combined with reflectance confocal laser scanning microscopy allows the "in situ" histological demonstration of oxygen free radical formation in live tissues. Here we present a case report, where oxidative stress is demonstrated on a histological level for the first time in human acute pancreatitis. A 44-year-old male patient suffering from acute exacerbation of his chronic pancreatitis developed a pancreato-pleural fistula with amylase-rich left pleural exudate causing respiratory compromise. Subsequent to an urgent thoracic decompression a distal pancreatectomy and splenectomy was performed with the closure of abdomino-thoracic fistula. The postoperative course was uneventful, except for a transient pancreatico-cutaneous fistula, which healed after conservative treatment. To carry out cerium capture oxygen free radical histochemistry the resected pancreas specimen was readily perfused with cerium-chloride solution through the arteries on the resection surface. Frozen sections were cut, E-, P-selectin, ICAM and VCAM were labeled by immunofluorescence. The tumor-free margin of an identically treated pancreas carcinoma specimen served as a control. Intrapancreatic oxidative stress and cellular adhesion molecule expression were detected by confocal laser scanning microscopy. Numerous pancreatic acini and neighboring capillaries showed oxygen free radical-derived cerium-perhy-droxide depositions corresponding to strong local oxidative stress. Acinar cytoplasmic reflectance signals suggested xanthine-oxidase as a source of oxygen free radicals. These areas presented considerably increased endothelial P-selectin expression with adherent, oxygen free radical-producing polymorphonuclear leukocytes displaying pericellular cerium-reflectance. Modest ICAM upregulation was noted, E-selectin and VCAM expression was negligible. The control pancreas specimen showed minimal oxidative stress with weak, focal P-selectin expression. The development of deleterious pancreatic oxidative stress was based on indirect evidence in human acute pancreatitis. To the best of our knowledge this is the first report demonstrating persistent intrapancreatic oxidative stress histologically in human acute pancreatitis. We have noted P-selectin overexpression with a preponderance in the areas of acinar oxidative stress.     

Malignant hypertension presenting as acute pancreatitis

We report a patient who was admitted to hospital with acute pancreatitis but who also had malignant phase hypertension. Whilst his alcohol intake was high, there was no objective evidence of alcoholic liver disease and no other underlying cause for pancreatitis was found. The pancreatitis may therefore have been due to pancreatic infarctions associated with fibrinoid necrosis. In all patients with acute pancreatitis, the diagnosis of malignant hypertension should be considered.     

重症急性胰腺炎的外科干预策略

重症急性胰腺炎病程中的"2次死亡高峰"是临床治疗中的一大挑战.早期为炎症反应期,应进行以维护器官功能为核心的多学科综合救治;后期以感染性并发症为主,外科医师对于外科干预指征、时机及方式的掌控尤为重要.重症急性胰腺炎的治疗已逐步形成为一个由多学科参与、个体化的综合治疗模式,临床中应建立以疾病为核心的综合救治平台.文章就近...     

Management of patients after recovering from acute severe biliary pancreatitis

Cholelithiasis is the most common cause of acute pancreatitis,accounting 35%-60% of cases. Around 15%-20% of patients suffer a severe attack with high morbidity and mortality rates. As far as treatment is concerned,the optimum method of late management of patients with severe acute biliary pancreatitis is still contentious and the main question is over the correct timing of every intervention. Patients after recovering from an acute episode of severe biliary pancreatitis can be offered alternative options in their management,including cholecystectomy,endoscopic retrograde cholangiopancreatography(ERCP) and sphincterotomy,or no definitive treatment. Delaying cholecystectomy until after resolution of the inflammatory process,usually not earlier than 6 wk after onset of acute pancreatitis,seems to be a safe policy. ERCP and sphincterotomy on index admission prevent recurrent episodes of pancreatitis until cholecystectomy is performed,but if used for definitive treatment,they can be a valuable tool for patients unfit for surgery. Some patients who survive severe biliary pancreatitis may develop pseudocysts or walled-off necrosis. Management of pseudocysts with minimally invasive techniques,if not therapeutic,can be used as a bridge to definitive operative treatment,which includes delayed cholecystectomy and concurrent pseudocyst drainage in some patients. A management algorithm has been developed for patients surviving severe biliary pancreatitis according to the currently published data in the literature.     

Clomiphene-induced acute pancreatitis without hypertriglyceridemia

Acute pancreatitis may be caused by drugs. In the literature, there are more than 260 different drugs that have been blamed for causing pancreatitis. Among these drugs, only 1 case has been reported as clomiphene-induced acute pancreatitis. However, in this single case, there was concomitant hypertriglyceridemia. We report the case of a woman who developed 2 attacks of acute pancreatitis without hypertriglyceridemia while receiving treatment with clomiphene.     

Plasma Exchange for Hypertriglyceridemic Acute Necrotizing Pancreatitis: Report of Two Cases

Abstract: We report two cases of hypertriglyceridemic necrotizing pancreatitis treated by plasma exchange (PE). The outcome of each case was quite different according to the timing of PE. A 36 year old man presented with abdominal pain, and a diagnosis of severe acute pancreatitis was made. His serum triglyceride (TG) level was 6,460 mg/dl. He did not undergo PE at first, however, his condition never improved and PE was performed 20 days after the onset of his illness. Finally, he died of multiple organ failure and sepsis. In contrast, a 52 year old man with acute necrotizing pancreatitis was referred to our department. He received PE quickly after hospital admission. His serum TG level, which was 3,540 mg/dl at hospital admission, dramatically returned to normal limits, and he was discharged from the hospital 62 days after admission. The prognosis of severe necrotizing pancreatitis due to hypertriglyceridemia is extremely poor. PE should be applied for the treatment of hypertriglyceridemic necrotizing pancreatitis immediately after its onset.