Cambridge Classification Research Articles

Screening for Early Pancreatic Neoplasia in High-Risk Individuals: A Prospective Controlled Study

Individuals with a strong family history of pancreatic cancer and persons with Peutz-Jeghers syndrome (PJS) have an increased risk for pancreatic cancer. This study screened for early pancreatic neoplasia and compared the pancreatic abnormalities in high-risk individuals and control subjects. High-risk individuals with PJS or a strong family history of pancreatic cancer were prospectively evaluated with baseline and 12-month computed tomography (CT) scan and endoscopic ultrasonography (EUS). If EUS was abnormal, EUS-fine-needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP) were performed. Surgery was offered to patients with potentially neoplastic lesions. Radiologic findings and pathologic diagnoses were compared. Patients undergoing EUS and/or ERCP for benign non-pancreatic indications were concurrently enrolled as control subjects. Seventy-eight high-risk patients (72 from familial pancreatic cancer kindreds, 6 PJS) and 149 control patients were studied. To date, 8 patients with pancreatic neoplasia have been confirmed by surgery or fine-needle aspiration (10% yield of screening); 6 patients had 8 benign intraductal papillary mucinous neoplasms (IPMNs), 1 had an IPMN that progressed to invasive ductal adenocarcinoma, and 1 had pancreatic intraepithelial neoplasia. EUS and CT also diagnosed 3 patients with 5 extrapancreatic neoplasms. At EUS and ERCP abnormalities suggestive of chronic pancreatitis were more common in high-risk patients than in control subjects. Screening EUS and CT diagnosed significant asymptomatic pancreatic and extrapancreatic neoplasms in high-risk individuals. IPMN should be considered a part of the phenotype of familial pancreatic cancer. Abnormalities suggestive of chronic pancreatitis are identified more commonly at EUS and ERCP in high-risk individuals.

Hyperechoic Abnormalities of Pancreatic Parenchyma On EUS in Patient with Normal Pancreatic Duct On ERP: Are They True Or Fake?

Background and Aim: Traditionally, the gold standard for the diagnosis of chronic pancreatitis (CP) has been either endoscopic retrograde pancreatography (ERP) and/or pancreatic function test. Recently, endoscopic ultrasonography (EUS) is considered a useful modality for the diagnosis of CP because of its ability to place the transducer in close proximity to the pancreas. Among patients with CP, EUS may reveal abnormal parenchyma in the form of hyperechoic changes, such as echogenic strands and hyperechoic foci. However, since these findings sometimes identified in patient with normal pancreatic duct on ERP, it will be confused whether it may diagnose early CP or not. The aim of this study was to investigate the implication of hyperechoic abnormalities on EUS in normal ERP. Patients and Methods: One hundred ten patients who were undergone both EUS and ERP within 2 months were enrolled, excluding in patient with pancreatic cancer, IPMN and lower biliary ductal cancer. CP was defined using the Cambridge classification of ERP findings. On EUS images, fine-reticular pattern as normal pancreatic parenchyma, and hyperechoic foci/strand as hyperechoic abnormalities were evaluated. Results: Normal/abnormal pancreatic duct on ERP was identified in 86 (78.2%) /24 (21.8%) patients, respectively. Fine-reticular pattern on EUS was seen in 76 (76/86: 88.3%)/3 (12/24: 50%) patients who had normal/abnormal ERP (p < 0.01). On the other, in 43 patients who had no EUS abnormalities, all patients (100%) were identified fine reticular pattern. Moreover, in 22 patients who had no fine-reticular pattern on EUS, all patients (100%) were identified parenchymal abnormalities. These results strongly suggested fine-reticular pattern indicated normal pancreatic parenchyma. On the basis of above findings, EUS abnormalities on normal ERP were investigated. Hyperechoic abnormalities on EUS were seen in 46 (53.7%) patients with normal ERP. In these 46 patients, fine-reticular pattern on EUS was seen in 36 patients, and none of them have become definite CP in the follow-up period. Conclusion: Hyperechoic EUS abnormalities (foci/strands) were not necessarily mean that presence of early chronic pancreatitis. Fine-reticular pattern is useful for differentiation whether hyperechoic abnormalities are true or fake.

Endosonographie bei chronischer Pankreatitis

Endoscopic ultrasound has continuously gained importance and has proven to be of clinical value in patients with chronic pancreatitis. In addition, the much lower complication rate when compared to ERCP has to be recognised. Some authors have indicated that endoscopic ultrasound in the evaluation of chronic pancreatitis is the imaging method of choice, depending on both ductal and parenchymal criteria, but there are still some limitations. The two major limitations of EUS preventing it being the "gold standard" in patients with chronic pancreatitis are the lack of standard criteria to be used, and adequate education. Endoscopic ultrasound is difficult to learn and therefore teaching has to be standardised. A general acceptance of the staging of chronic pancreatitis using a catalogue based on criteria compatible to the Cambridge classification is required. Difficulties in evaluating parenchymal criteria with the exception of "indicative" calcifications, depend on the differentiation of the normal ageing process from sequelae of acute pancreatic, ethyl-toxic fibrosis and early stages of chronic pancreatitis. In addition, the differentiation of hypoechoic and cystic lesions as inflammatory changes or neoplastic tumours is still difficult; complementary imaging methods also have low sensitivity in this area. In conclusion, there is no doubt that endoscopic ultrasound has proven to be of value using an interdisciplinary approach in the evaluation and therapy of pseudocysts, peripancreatic necrosis, and pancreatic and bile duct obstruction.

Quantification of pancreatic exocrine function with secretin-enhanced magnetic resonance cholangiopancreatography: normal values and short-term effects of pancreatic duct drainage procedures in chronic pancreatitis. Initial results

The aim of this study was to quantify pancreatic exocrine function in normal subjects and in patients with chronic pancreatitis (CP) before and after pancreatic duct drainage procedures (PDDP) with dynamic secretin-enhanced magnetic resonance (MR) cholangiopancreatography (S-MRCP). Pancreatic exocrine secretions [quantified by pancreatic flow output (PFO) and total excreted volume (TEV)] were quantified twice in ten healthy volunteers and before and after treatment in 20 CP patients (18 classified as severe, one as moderate, and one as mild according to the Cambridge classification). PFO and TEV were derived from a linear regression between MR-calculated volumes and time. In all subjects, pancreatic exocrine fluid volume initially increased linearly with time during secretin stimulation. In controls, the mean PFO and TEV were 6.8 ml/min and 97 ml; intra-individual deviations were 0.8 ml/min and 16 ml. In 10/20 patients with impaired exocrine secretions before treatment, a significant increase of PFO and TEV was observed after treatment (P<0.05); 3/20 patients presented post-procedural acute pancreatitis and a reduced PFO. The S-MRCP quantification method used in the present study is reproducible and provides normal values for PFO and TEV in the range of those obtained from previous published intubation studies. The initial results in CP patients have demonstrated non-invasively a significant short-term improvement of PFO and TEV after PDDP.

EUS-guided Trucut biopsy of suspected nonfocal chronic pancreatitis

The diagnosis of early chronic pancreatitis (CP) is difficult, and the role of EUS-FNA cytology for this indication remains unclear. The aim of this study is to determine the utility and the safety profile of EUS-guided Trucut biopsy (EUS-TCB) for the histologic diagnosis of suspected nonfocal CP. After radial EUS, patients with suspected CP (> or =3 EUS criteria) underwent attempted transgastric EUS-TCB of the pancreas. Histopathologic specimens were examined by one pathologist and were classified as nondiagnostic, normal pancreas, and probable or definite CP. Within 1 week after EUS, ERCP was performed by an endoscopist blinded to the EUS results. The severity of CP by ERCP was stratified by the Cambridge classification. Agreement between tests for the diagnosis of CP was evaluated by a kappa statistic. Of 45 patients screened, 15 declined and 30 (12 men and 18 women, mean age 44 years) underwent diagnostic EUS. Of these, 18 (60%) had suspected CP and 16 underwent attempted biopsy. Calcific pancreatitis in two patients precluded EUS-TCB. EUS-TCB results were as follows: probable CP (1), normal pancreas (8), nondiagnostic (6), device malfunction (1). Complications after EUS-TCB occurred in two patients with normal pancreatic biopsies were the following: acute pancreatitis (1) and abdominal pain without pancreatitis (1), both of whom were hospitalized and discharged within 23 hours. Six patients refused ERCP and two (per protocol) did not undergo ERCP. For the remaining 22, agreement between diagnostic EUS and ERCP was moderate (kappa, 0.40). Agreement between EUS and ERCP with EUS-TCB were poor (kappa, 0) and fair (kappa, 0.25), respectively. Transgastric EUS-TCB of suspected nonfocal CP infrequently demonstrates histologic CP in clinically suspected disease. Because of potential complications and limited diagnostic yield, this technique is not currently recommended for evaluation of these patients.

HEREDITARY PANCREATITIS IN CHILDREN

The etiology of chronic pancreatitis (CP) in children is varied and includes gene mutations, i.e. cationic trypsinogen gene mutations (PRSS1). Aim: The aim of this study was to assess prevalence of cationic trypsinogen gene mutations in children with chronic or acute recurrent pancreatitis (ARP) and its influence on clinical course of pancreatitis. Methods and Results: We evaluated 94 children with CP or ARP aged 3-18 yrs. PRSS1 gene mutations were found in 12 children (12,8%) with CP; 11 girls and 1 boy (aged 3,6-16, 3 years); 6 children had R122H/- mutation, 5 children had R122C/- and one child N29I/-. 11 children had positive family history of pancreatitis. In two patients with PRSS1 mutations, pancreas divisum was diagnosed. Two additional mutations were found in 2 patients (one patient had SPINK1 mutation N34S/-, and second one 5T variant in CFTR gene). There was no difference in age of the disease onset between patients with hereditary pancreatitis and patients without PRSS1 mutations (7.86 years vs. 9.01 years, NS). Pancreatitis grading, according to the Cambridge Classification System was 2,83° grade in PRSS1 group vs.1,45° in the group without mutations (p < 0,05). Conclusions: 1. Cationic trypsinogen gene mutations (PRSS1) are common in children with chronic pancreatitis. 2. Children with CP associated with PRSS1 have worst clinical course of the disease.

Prospective Comparison of EUS, ERCP, and EUS-Guided True Cut Biopsy (EUS-TCB) for Suspected Chronic Pancreatitis

Background: Without histology, the diagnosis of chronic pancreatitis (CP) is made by clinical presentation and radiographic data. While EUS-FNA may be used to aid the diagnosis, the role of cytology for this indication remains debatable. Aims: 1) determine the utility and safety profile of a novel EUS-guided tru-cut biopsy (EUS-TCB) device (Quick-Core, Wilson-Cook Medical, Inc.) for the diagnosis of suspected chronic pancreatitis; 2) Compare EUS and ERCP to each other and individually to EUS-TCB for suspected CP. Methods: Inclusion criteria: Subjects between 18-60 with >3 months of upper abdominal pain and suspected CP (regardless of severity). Exclusion criteria: prior pancreatic or upper GI tract surgery, thrombocytopenia, anemia, coagulopathy, CAD, pancreatic cancer or cyst, or acute pancreatitis or pancreatic stent within the previous 3 months. Subjects with ≥3 EUS criteria for CP within the body and neck on radial EUS underwent attempted transgastric EUS-TCB followed within one week by ERCP. The endoscopist performing ERCP was blinded to the EUS results. All pathology was examined by one expert pathologist. The severity of CP was stratified by Cambridge classification for ERCP and by the number of ductal/parenchymal criteria present at EUS (normal: 0; equivocal: 1-2, mild: 3-4; moderate: 5-6; severe >6). Agreement between EUS and ERCP was evaluated by a weighted kappa statistic. Results: Of 29 subjects screened, 18 were enrolled (11 male, 18 Caucasian; mean age: 42), all of whom underwent EUS. Of these, 9 had ≥3 EUS criteria and 8 underwent attempted EUS-TCB. One subject with calcific pancreatitis could not be safely biopsied. EUS-TCB results: normal pancreas (n=5; mean biopsy length: 3.4 mm), nondiagnostic (n=2), device malfunction (n=1). No biopsies were diagnostic for CP. Complications from EUS-TCB: acute pancreatitis (n=1) and abdominal pain without pancreatitis (n=1), both of whom were discharged after a one day hospitalization. Five refused ERCP following EUS; the remaining 13 underwent ERCP without complications. Of the 5 with normal histology by EUS-TCB, ERCP was normal (n=1) or showed mild (n=3) or moderate CP (n=1). Agreement between EUS and diagnostic ERCP was moderate (kappa: 0.55, 95% CI: 0.24-0.86). Conclusion: In this preliminary study, EUS-TCB was relatively safe but did not demonstrate histologic CP with clinically suspected early disease. Agreement between EUS and ERCP was moderate. This study was supported by a grant from Wilson-Cook Medical, Inc.

Alterations of bone mineral density and bone metabolism in patients with various grades of chronic pancreatitis

The aim of this study was to examine bone mineral density (BMD) and bone metabolism in patients with chronic pancreatitis to determine if increased severity of the disease would correlate with increased bone loss. Between October 1999 and September 2000, we investigated 42 patients with an average age of approximately 53 years suffering from chronic pancreatitis, as well as 20 healthy male controls with an average age of 49 years. Dual energy x-ray absorptiometry (DEXA) was performed on patients and controls, and serum levels of parathyroid hormone (PTH), osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (CICP), bone-specific alkaline phosphatase (BAP), 1,25(OH)2 vitamin D3 and 25(OH) vitamin D3, as well as fecal elastase 1 were also determined. The severity of chronic pancreatitis in patients was determined via endoscopic retrograde cholangiopancreatography (ERCP) and assigned to 1 of 3 grades based on the Cambridge classification. BMD of patients with chronic pancreatitis was markedly decreased compared to controls (means in patients: DEXA lumbar vertebra anterior/posterior (LV ap) 96.8% ± 4.2%, DEXA Ward's triangle (WARD) 92.2% ± 5.2%; controls: DEXA LV ap 98.7% ± 3.7%, DEXA WARD 97.1% ± 3.1%; P <.05 and P <.0001) and correlated with the various Cambridge-grades (DEXA LV ap and DEXA WARD, P <.01). Fecal elastase 1 showed sensitivities of 14%, 87%, and 95% for the Cambridge-grades I, II, and III, respectively, and correlated with this classification of severity of chronic pancreatitis (P <.01). Furthermore, fecal elastase 1 of patients correlated the same way with both D3-vitamins (P <.01), as well as with parameters of BMD (P <.01). If fecal elastase 1 in patients was below 200 μg/g, then the BMD and vitamin D3 values were also significantly decreased compared to those with fecal elastase 1 above 200 μg/g. In patients with Cambridge grades II and III 1,25(OH)2D3 was markedly decreased (26.7 ± 7.7 pg/mL and 27.6 ± 9.0 pg/mL) compared to those with Cambridge grade I (38.0 ± 10.5 pg/mL; between I and II, P =.027; between I and III, P =.033). 25(OH)D3 was not significantly different within the various Cambridge groups (P =.07). Compared to controls, both D3 vitamins, as well as fecal elastase 1, were extremely low (means in patients: fecal elastase 1, 140.7 ± 75.7 μg/g; 1,25(OH)2D3, 29.9 ± 9.5 pg/mL; 25(OH)D3, 26.7 ± 9.7 nmol/L; controls: fecal elastase 1, 694.9 ± 138.6 μg/g; 1,25(OH)2D3, 67.5 ± 4.3 pg/mL; 25(OH)D3, 69.5 ± 13.5 nmol/L). A significant correlation was observed between increased severity of chronic pancreatitis based on both endoscopic retrograde cholangiopancreatography and levels of fecal elastase 1, with decreased circulating levels of vitmain D3 and decreased BMD. This supports a connection between the inflammatory destruction of the pancreas (Cambridge classification), exocrine pancreatic insufficiency (fecal elastase 1), altered levels of vitamin D metabolites, and loss of skeletal mass. © 2003 Elsevier Inc. All rights reserved.

Chronic Pancreatitis and Diabetes mellitus

Background: Pancreatic exocrine dysfunction has been described frequently in IDDM and NIDDM patients. Most authors tried to explain this finding as a diabetic complication. On the other hand, diabetes secondary to chronic pancreatitis (CP) might be more common than believed so far. Aim of the Study: In this study we evaluated pancreatograms of patients with known diabetes mellitus in order to detect ductal morphology changes characteristic for CP. Methods: Consecutive diabetic patients admitted for ERCP for different reasons were evaluated retrospectively concerning ERCP findings, especially pancreatic duct changes (Cambridge classification), diabetes type, duration and therapy. Results: 156 patients (76 male, 80 female; mean age 60 years (19–93)) were studied (38 IDDM; 118 NIDDM). Pancreatic ducts were classified as normal in 23.3%, CP°I in 22.7%, CP°II in 32.7% and CP°III in 21.3%. The duct changes did not correlate with diabetes type (p = 0.19), diabetes duration (p = 0.38), diabetes therapy (p = 0.5) or age (p = 0.48). Conclusion: Since CP should be defined by morphological and functional changes, it must be concluded that a substantial number of patients with a primary diagnosis of diabetes mellitus may have CP as a concomitant disease or, more likely, as a cause for their diabetic state.

Endoscopic ultrasonography (EUS) and fine-needle aspiration (FNA) cytology for diagnosis of chronic pancreatitis.

Previous studies have shown that endoscopic ultrasonography (EUS) sensitively detects morphologic abnormalities due to chronic pancreatitis. However, morphologic EUS findings have limited specificity, particularly at the early stages of chronic pancreatitis. Our aims were to study pancreatic morphology and inflammation in patients with chronic pancreatitis, using EUS and fine-needle aspiration cytology (EUS-FNA), and to compare the results with those of endoscopic retrograde cholangiopancreatography (ERCP) and pancreatic function tests. 37 patients (48 +/- 13 years) with clinical symptoms and laboratory test findings suggestive of chronic pancreatitis were prospectively studied. Patients with malignancy or major concomitant disorders were excluded. Clinical evaluation included indirect pancreatic function tests. Morphologic criteria for chronic pancreatitis included echo-intense septae/echo-reduced foci (i. e. pseudolobularity), ductal irregularities, and calcifications. EUS-FNA was performed in 27/37 patients, by means of the Hitachi FG34-UX echo endoscope and a 22-gauge needle, and tissue specimens were submitted for standard cytological evaluation. ERCP served as reference in all patients, using the Cambridge classification. 31 patients had chronic pancreatitis while six had normal findings at ERCP. EUS showed morphologic abnormalities of the pancreas in 33 patients. Morphologic abnormalities alone reached a sensitivity of 97 % for chronic pancreatitis with a specificity of only 60 %, while the positive predictive value (PPV) was 94 %, and the negative predictive value (NPV) was 75 %. EUS-FNA increased the negative predictive value to 100 % and the specificity to 67 %. On average, 2.3 needle passes were necessary to obtain sufficient amounts of tissue. The correlation of EUS findings with pancreatic function tests was poor. EUS results were in agreement with regard to the severity of chronic pancreatitis in 5/8 patients with grade I disease, in 11/13 patients with grade II, and in 10/10 patients with grade III disease. Minor complications occurred in two patients (7 %). EUS is as sensitive and effective as ERCP in the detection of chronic pancreatitis, particularly when only mild disease is present. However, EUS findings have limited specificity, particularly in patients with mild disease. EUS-FNA with cytology is safe and improves the negative predictive value. Negative EUS-FNA findings rule out chronic pancreatitis, but cytological investigation alone does not improve the specificity of EUS findings, suggesting that further improvements in tissue sampling and analysis are necessary to support routine use of FNA in patients with chronic pancreatitis.

Outcome of Surgical Treatment of Chronic Pancreatitis Associated with Sphincter of Oddi Dysfunction

The clinical management of patients with chronic pancreatitis (CP) associated with sphincter of Oddi dysfunction (SOD) presents many challenges. The aim of this study was to evaluate patient outcome after surgical management of CP associated with SOD intractable to medical management. The records of patients with CP and SOD who underwent surgical treatment between 1994 and 1998 were retrospectively reviewed and analyzed. Manometry of biliary and pancreatic ducts was performed. Basal pressures were considered abnormal if > or = 40 mm Hg for at least 30 seconds. Endoscopic retrograde cholangiopancreatography, endoscopic ultrasound, and clinical criteria were utilized in the diagnosis of CP. Quality-of-life issues were assessed. Twenty-nine patients were identified (21 women and eight men) with a mean age of 43.3 years (range 24-54). Mean basal biliary and pancreatic sphincter pressures were 155.1 and 90.4 mm Hg respectively. Chronic pancreatitis was graded as mild in nine patients, moderate in six, severe in two, and normal or equivocal in 12 patients according to the Cambridge classification. A Whipple procedure was performed in 17 (59%) patients, lateral pancreaticojejunostomy in nine (31%), and distal resections or a combination of procedures in three (10%). The morbidity and mortality rates were 21 and 0 per cent respectively. Mean follow-up was 30 months (range 3-48). Pain relief ranging from fair to excellent was seen in 83 per cent of patients with pain scores decreasing from an average of 9 (scale 1-10) before surgery to 3 postoperatively. Seventy per cent maintained their weight, 45 per cent continued to require pancreatic enzyme supplementation, and there were no changes in the status of diabetes. Rehospitalizations for recurrent pancreatitis or persistent pain were necessary in 24 per cent of patients. Surgical management of patients with CP and SOD who fail medical management is safe and effective in most patients. Operative morbidity and mortality are low, and the majority of patients have improvement in pain, although some require rehospitalization for recurrent pancreatitis and chronic pain.

Role of differential neuroaxial blockade in the evaluation and management of pain in chronic pancreatitis

OBJECTIVES: Chronic pancreatic pain is difficult to treat. Surgical and medical therapies directed at reducing pain have met with little long-term success. In addition, there are no reliable predictors of response including pancreatic duct diameter. A differential neuroaxial blockade allows characterization of chronic abdominal pain into visceral and nonvisceral pain origins and may be useful as a guide to the treatment. Pain from an inflamed, and scarred pancreas should be visceral in origin. The purpose of our study was to determine the frequency with which patients with chronic pancreatitis have visceral pain and whether our modified differential neuroaxial blockade technique using thoracic epidural analgesia can accurately predict which patients will respond to medical or surgical therapy. METHODS: We retrospectively reviewed the medical records of patients with a firmly established diagnosis of chronic pancreatitis (Cambridge classification, calcifications) who had undergone a differential neuroaxial block for their chronic abdominal pain evaluation. Patient demographics and medical or surgical treatment for pancreatic pain was recorded. Response to therapy was defined by a 50% reduction in pain by verbal response score. RESULTS: A total of 23 patients were identified. Alcohol was the most common etiology for chronic pancreatitis (15 of 23, 55%). Surprisingly, the majority of chronic pancreatitis patients had nonvisceral pain (18 of 23, 78%) and only 22% (5 of 23) had visceral pain by differential neuroaxial block. Four of five patients (80%) with visceral pain responded to therapy, whereas only 5 of 17 (29%) of patients with nonvisceral pain responded. CONCLUSIONS: Surprisingly, patients with chronic pancreatitis commonly have nonvisceral pain. Differential neuroaxial blockade can predict which patients will respond to therapy.

Role of differential neuroaxial blockade in the evaluation and management of pain in chronic pancreatitis.

Chronic pancreatic pain is difficult to treat. Surgical and medical therapies directed at reducing pain have met with little long-term success. In addition, there are no reliable predictors of response including pancreatic duct diameter. A differential neuroaxial blockade allows characterization of chronic abdominal pain into visceral and nonvisceral pain origins and may be useful as a guide to the treatment. Pain from an inflamed, and scarred pancreas should be visceral in origin. The purpose of our study was to determine the frequency with which patients with chronic pancreatitis have visceral pain and whether our modified differential neuroaxial blockade technique using thoracic epidural analgesia can accurately predict which patients will respond to medical or surgical therapy. We retrospectively reviewed the medical records of patients with a firmly established diagnosis of chronic pancreatitis (Cambridge classification, calcifications) who had undergone a differential neuroaxial block for their chronic abdominal pain evaluation. Patient demographics and medical or surgical treatment for pancreatic pain was recorded. Response to therapy was defined by a 50% reduction in pain by verbal response score. A total of 23 patients were identified. Alcohol was the most common etiology for chronic pancreatitis (15 of 23, 55%). Surprisingly, the majority of chronic pancreatitis patients had nonvisceral pain (18 of 23, 78%) and only 22% (5 of 23) had visceral pain by differential neuroaxial block. Four of five patients (80%) with visceral pain responded to therapy, whereas only 5 of 17 (29%) of patients with nonvisceral pain responded. Surprisingly, patients with chronic pancreatitis commonly have nonvisceral pain. Differential neuroaxial blockade can predict which patients will respond to therapy.

Pathological pancreatic exocrine function and duct morphology in patients with cholelithiasis.

Most authors claim alcohol consumption to be the only relevant reason for chronic pancreatitis. However, gallstones might cause this disease, as they do cause acute pancreatitis. In this study 91 gallstone patients and 94 age-matched controls were investigated concerning exocrine pancreatic function (fecal elastase-1 concentrations). Furthermore x-rays of 100 consecutive ERCP patients were evaluated for differences concerning pancreatic duct changes between patients with and without evidence of cholelithiasis. Pathological elastase 1 levels were more frequent in gallstone patients (30,8%) as compared to age-matched controls (19%). Symptoms such as upper abdominal pain, bloating, and fat intolerance were reported more often in gallstone patients. In ERCP of gallstone patients (N = 60), 77% were found to have chronic pancreatitis according to the Cambridge classification, while in nongallstone-patients (N = 32) 47% had chronic pancreatitis. In conclusion, according to these data a pathophysiological connection between gallstones and chronic pancreatitis appears to be probable.

4560 Assessment of chronic pancreatitis by using endoscopic ultrasonography and fine-needle aspiration cytology compared with ercp and pancreatic function tests.

Background: Previous studies showed that endoscopic ultrasonography (EUS) can sensitively detect structural inflammatory changes of the pancreas. However, little is known about the specificity and clinical impact of EUS findings in chronic pancreatitis (cP). Therefore, we studied the morphology of the pancreas in patients with cP by using EUS techniques and fine-needle aspiration cytology (FNA), and we compared the EUS results to ERCP and pancreatic function tests. Materials/Methods: 37 patients with clinical symptoms and laboratory tests suggestive of cP (48±13 years) were prospectively studied. Patients with malignancy or major concomitant disease were excluded. EUS was carried out 10±3 days after the resolution of clinical signs of pancreatitis, and FNA was performed during EUS in 24 patients. EUS criteria for cP included the presence of echointense septae and echoreduced foci (=pseudolobularity), ductal irregularities, and calcifications. ERCP served as reference in all patients using the Cambridge classification. The clinical work-up also included fecal elastase and urine pancreolaureate tests. Results: 31 patients had cP, while 6 had normal findings during ERCP. EUS showed morphologic abnormalities in 32 patients, while ERCP revealed pathologic findings in only 31 patients. The combination of EUS/FNA versus ERCP reached a sensitivity of 100% with a specificity of 83%. Based on the presence of pseudolobularity alone, EUS reached a sensitivity of 96% with a specificity of only 72% for the presence of chronic pancreatitis, while the positive predictive value (PPV) was 93%, and the negative predictive value (NPV) was 83%. Based on 3 EUS criteria including ductal irregularities, the specificity decreased to 46%, while the sensitivity reached 97%. Compared with pancreatic function tests, EUS reached a sensitivity of only 86% with a specificity of 73%. EUS was in agreement with the severity of chronic pancreatitis in 6/8 patients with grade I, in 11/13 patients with grade II, and in 10/10 patients with grade III. Conclusions: EUS is a highly sensitive tool to detect morphologic abnormalities of the pancreas. However, the EUS findings are unspecific, which is probably due to postinflammatory organ abnormalities that may resolve completely over time. FNA improves the specificity and should thus be performed routinely during EUS. The association between morphologic findings and pancreatic function is poor.

3711 PROSPECTIVE EVALUATION OF ENDOSCOPIC ULTRASONOGRAPHY AND ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY IN THE DIAGNOSIS OF CHRONIC PANCREATITIS IN AN ADOLESCENT POPULATION.

Chronic pancreatitis (CP) in its early stages may defy diagnosis despite existing diagnostic modalities. Endoscopic retrograde cholangiopancreatography, Secretin test, conventional ultrasound, and computed tomography are insensitive in detecting the early stages of CP. AIM: To determine if EUS high resolution imaging allows for the detection of CP when compared to clinical history, ERCP, and Secretin test. METHOD: Thirty-two consecutive patients (22-w, 10-m, age range 13-19, mean 16.6) over a seven year period with acute or recurrent pancreatitis underwent ERCP. ERCP evaluation of chronic pancreatitis was determined by the Cambridge Classification. EUS evaluated: 1. Parenchymal changes: echogenic foci (calcifications), prominent interlobular septae (fibrosis), atrophy, heterogeneous parenchyma, lobular gland margin, microcystic lesions; and 2. Ductal changes: Dilation, stricture, irregularity, echogenic wall (fibrosis), side branch ectasia, echogenic foci (stone). EUS criteria for CP included: mild (1-2 features), moderate (3-5 features present), severe (>than 5 features). RESULTS: Abnormal studies were seen by EUS=26 and ERCP=18. Agreement between EUS specific criteria and ERCP was excellent for normal (83%), moderate (89%),and severe (100%) CP but poor for mild disease by EUS criteria (33.3%). CONCLUSION: Using the above EUS criteria, EUS may assist in the diagnosis of CP not established by clinical history or ERCP. Excellent agreement can be expected between EUS and ERCP diagnosis of CP with the exception of mild changes noted on EUS. Longterm follow-up of CP patients with mild EUS changes will determine the validity of EUS in diagnosing the early changes of CP.

4559 Long term follow-up of early chronic pancreatitis diagnosed at endoscopic ultrasonography.

Aim : The diagnosis of early chronic pancreatitis (ECP) remains difficult and endoscopic ultrasonography (EUS) features are still controversial. The aim of this study was to evaluate the long term follow-up of patients with ECP diagnosed at EUS. Methods : Between 1994 and 1998, 37 patients were diagnosed to have ECP at EUS. All experienced at least one episode of non biliary acute pancreatitis. None had evidence of pancreatic stone on plain film of the abdomen or on CTscanner. The ECP were classified as group A (possible ECP with either parenchymal signs or ductal signs), as group B (probable ECP with both parenchymal and ductal signs) and as group C (certain ECP with pancreatic stones). Results : 11 patients were lost to follow-up, 26 men with median age of 46.5 (23-70) years and median alcohol consumption of 76 ( 0-150) g per day, have been followed for a median duration of 37 (1-94).months. - At the initial examination, 10 patients belonged to group A, 4 to group B and 12 to group C. The pancreatographies (n=24) according to the Cambridge classification were 7 cases in stage 0, 4 cases in stage 1 , 4 cases in stage 2 and 9 cases in stage 3. - At the end of the follow-up, 4 patients underwent surgery (pseudotumorous chronic pancreatitis in 2 cases, duodenal cystic dystrophy in 1 case, and pancreatic cancer complicating chronic pancreatitis in 1 case). 26 patients had clinical evaluation : 12 remained unchanged, 12 had improved health status and 2 still experienced clinical disorders (pain, weight-loss). The final diagnosis of certain ECP was yeldied in 6 out of 10 patients of the group A, in 3 out of 4 patients of the group B and in 9 out of the 12 patients of the group C. Conclusion : The positive predictive value of EUS signs of ECP was 64% in case of possible or probable ECP and 75% in case of certain ECP.

Prospective assessment of the ability of endoscopic ultrasound to diagnose, exclude, or establish the severity of chronic pancreatitis found by endoscopic retrograde cholangiopancreatography

Background: Our aim was to verify endoscopic ultrasound (EUS) accuracy to diagnose, rule out, and establish the severity of chronic pancreatitis found by endoscopic retrograde cholangiopancreatography (ERCP). Methods: Patients undergoing ERCP for unexplained abdominal pain and/or suspected chronic pancreatitis underwent EUS. EUS was performed by experienced operators who were aware of the history but blinded to ERCP results. Chronic pancreatitis was defined using the Cambridge classification: 0 to 1 = “normal,” 2 to 4 = “all chronic pancreatitis,” 3 to 4 = “moderate to severe chronic pancreatitis.” The number of EUS criteria required to obtain sensitivity, specificity, positive and negative predictive values ≥ 85% was determined. EUS criteria for chronic pancreatitis are hyperechoic foci, hyperechoic strands, lobularity, hyperechoic duct, irregular duct, visible side-branches, ductal dilation, calcification, and cysts. Results: One hundred twenty-six patients underwent EUS and ERCP. EUS was highly sensitive and specific (> 85%) depending on the number of criteria present. Chronic pancreatitis is likely (PPV > 85%) when more than two criteria (for “all chronic pancreatitis”) and more than six criteria (for “moderate to severe chronic pancreatitis”) are present. “Moderate to severe chronic pancreatitis” is unlikely (NPV > 85%) when fewer than three criteria are present. Independent predictors of chronic pancreatitis were “calcification” ( p = 0.000001), history of alcohol abuse ( p = 0.002), and the total number of EUS criteria ( p = 0.008). Conclusions: EUS can accurately diagnose, rule out, and establish the severity of chronic pancreatitis found by ERCP. (Gastrointest Endosc 1998;48:18-25.)

Pancreatic ductal changes in HIV-infected patients

Background: AIDS-related sclerosing cholangitis occurs in patients with advanced immunodeficiency, but ductal pancreatic alterations have not been evaluated in large series. Methods: Twenty-nine consecutive patients with a mean age of 33 years underwent ERCP for biliary work-up. Complete pancreatography was obtained in 28 patients. Serum levels of amylase were increased in 17 patients prior to ERCP. The mean duration of HIV infection was 6.1 years (range 3 to 10 years). Results: Fifteen patients (53.6%) had pancreatographic changes classified according to the Cambridge classification (stage 1, 4 cases; stage 2, 7 cases; stage 3, 4 cases). Dilatations, irregularities, short stenoses of the main pancreatic duct, and irregularities of side branches were the most frequent abnormalities. Fourteen of these 15 patients (93.3%) had cholangitis and a CD4 cell count of less than 60 per cubic millimeter. Risk factors for pancreatic damage were similar in patients with and without pancreatographic changes. Opportunistic infection occurred in 14 of 15 patients with pancreatographic changes (candida, cytomegalovirus, cryptosporidia, microsporidia, and mycobacteria). Conclusion: Abnormal pancreatographies were found in about half of the HIV-infected patients who underwent ERCP. The pancreatographic features were suggestive of chronic pancreatitis and were closely related to the presence of AIDS-related sclerosing cholangitis. (Gastrointest Endosc 1997;45:59-63.)

Outcome audit in plastic surgery

Abstract Plastic Surgery Outcome Audit has until now been limited to studies of individual conditions. The Department of Plastic Surgery at Addenbrooke's Hospital, Cambridge, has developed an objective outcome classification applicable to all plastic surgery procedures. The four end-result categories — aesthetic appearance; physical function; tumour clearance; and surgical complications — are each graded in clear stages from 1 (excellent result) to 4 (result requiring re-operation) in a system which is easy to apply to every patient. The development and potential use of this classification are discussed. The Cambridge Classification is used in conjunction with diagnostic codes, which can be simple like the Logbook codes used by British Trainees or more complex, such as Read codes.