Does endoscopic therapy favorably affect the outcome of patients who have recurrent acute pancreatitis and pancreas divisum?
Explore the source record for details and available documents.
Acute Disease↗
Biomedical subjects
Eugene P DiMagno
Publications and source records attributed to Eugene P DiMagno.
'Good mentorship is invaluable' - an interview with Dr. Eugene P. DiMagno. Interview by Martin E. Fernandez-Zapico.
Dr. DiMagno is internationally renowned for his contributions to almost all areas of pancreatology. He helped pioneer discoveries about normal pancreatic function, enzyme-based treatment of exocrine pancreatic insufficiency as well as methods of diagnosing pancreatitis and pancreatic cancer, including the development of function tests and endoscopic ultrasound. Answering Martin Fernandez-Zapico's questions, he stresses the importance of good mentorship and gives us a glimpse of his life and work.
Animals↗
A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma.
BACKGROUND: To compare operative morbidity, mortality, quality of life, and survival after pancreatoduodenectomy (PD) versus pancreatoduodenectomy with extended lymphadenectomy (PD/ELND) in patients with resectable pancreatic cancer. METHODS: From May 1997 to July 2003 there were 132 patients with biopsy examination-proven or suspected adenocarcinoma of the pancreatic head who agreed to participate in a single-institution, prospective, randomized trial. If resectable at operation, patients then were randomized to standard PD (40 patients) or PD/ELND (39 patients). Quality of life was assessed by using the Functional Assessment of Response to Cancer Therapy specific to the pancreas. Morbidity, mortality, and survival were analyzed. RESULTS: Demographics and pathologic characteristics for both groups were similar. When comparing PD/ELND with standard PD, the median operating time was greater for the PD/ELND group (7.6 h vs 6.2 h, P < .01), blood transfusion more likely (44% vs 22%, P < .05), and the median number of lymph nodes resected was greater (36 vs 15 nodes, P < .01). Morbidity and mortality rates were comparable. Median durations of stay were 11 and 10.5 days (P = NS), respectively. There were no significant differences in 1-year (71% vs 82%), 3-year (25% vs 41%), 5-year (16.5% vs 16.4%), and median (19 vs 26 mo) survival (P = .32). At 4 months postoperatively, diarrhea, body appearance, and bowel control scored lower on the Functional Assessment of Response to Cancer Therapy specific to the pancreas after PD/ELND (P < .05). CONCLUSIONS: Although a much larger study would have more power to compare statistically the survival between groups, both the decrement in quality of life and similar studies showing no survival difference make PD/ELND unattractive for further prospective investigation.
Adenocarcinoma↗
Chronic pancreatitis.
PURPOSE OF REVIEW: As in our previous reviews, we endeavor to review important new observations in chronic pancreatitis made in the past year. We included articles, including review articles, only if they contained new observations or readdressed old questions and provided new insights into old and new concepts. RECENT FINDINGS: Important observations include the following: (1) Strong association between cystic fibrosis transmembrane regulator dysfunction/mutations and 'recurrent acute pancreatitis', particularly in patients with pancreas divisum (2) Pancreas divisum may be incidental finding in recurrent acute pancreatitis (3) Smoking increases risk of chronic pancreatitis (4) Coxsackie B virus may increase severity of alcoholic chronic pancreatitis (5) CD4+ T cells and an immune reaction against amylase may play a role in pathogenesis of autoimmune pancreatitis (6) 2-(18F)-Fluro-2-deoxy-D-glucose positron emission tomography might be useful to detect pancreatic cancer in chronic pancreatitis patients at risk for developing pancreatic cancer, but contrast-enhanced Doppler ultrasound or endosonography may be as sensitive and better than contrast enhanced computed tomography (7) Superiority of surgery vs endotherapy for long term pain relief and weight gain in painful chronic pancreatitis (8) Early treatment of pain and malabsorption may improve life quality (9) Antifibrogenesis and fibrolytic agents as potential therapies. SUMMARY: Ongoing basic and clinical research this past year has further characterized genetic, molecular and clinical aspects of chronic pancreatitis. The advent of predictable and lasting treatments of chronic pancreatitis is most likely to appear on the wings of carefully conducted studies targeting genetic and molecular mechanisms of chronic pancreatitis, particularly pancreatic fibrogenesis.
Global Health↗
Chronic pancreatitis.
PURPOSE OF REVIEW: Clinicians are learning more about chronic pancreatitis but are entering an era of some confusion, primarily driven by uncovering new etiologies of chronic pancreatitis. Ideally, this knowledge will lead to better diagnosis and treatment, and abandonment of ill-conceived treatments. In contrast with previous reviews, this review highlights select contributions this year that may develop into true advances in chronic pancreatitis. RECENT FINDINGS: Small steps have been made to understand better the molecular basis of chronic pancreatitis. Diagnosis of early chronic pancreatitis remains challenging. Rapid diagnosis by combining endoscopy and a direct stimulatory test of pancreatic function may lead to more widespread use of function testing, but this test is not ready for clinical use. Application of microarray and proteomic technologies may aid future diagnosis of chronic pancreatitis. The failure to account clearly for the phenotype of patients with chronic pancreatitis may confound delineating the etiologies of chronic pancreatitis. Clinical description and studies of autoimmune pancreatitis have led to the realization that steroids are an effective treatment for this form of chronic pancreatitis. Genetic-based studies have provided insight into the pathogenic mechanisms of chronic pancreatitis. Investigation of the role of stellate cells, an essential component fibrogenesis, has led to identification of potential novel treatments for chronic pancreatitis. SUMMARY: Ongoing basic and clinical research this past year has characterized further the histologic, genetic, molecular, and clinical aspects of chronic pancreatitis, efforts that may translate into novel therapies once well-designed, controlled studies have been performed.
Journal Article↗
Primer on medical genomics. Part XIII: Ethical and regulatory issues.
Ethics in the new genomics era has become an increasingly complex subject that often arouses passion and confusion. Although 50 years have elapsed since the elucidation of the DNA molecule, the recent near-complete sequencing of the human genome has sharply accelerated the incorporation of genetics into the medical mainstream. Along with these scientific advances, however, have surfaced challenges, liabilities, and issues regarding the processing and management of genetic information as they relate to core ethical principles such as respect for autonomy, beneficence, nonmaleficence, and justice. Institutions and state and federal governments have initiated systematic and preemptive measures in education, resource development, and protective legislation to address these cardinal ethical issues. Genetic research is also being scrutinized carefully by institutional review boards, an activity that should not be perceived as being adversarial but rather as a protective shield for investigators and research participants alike. Ultimately, it is hoped that genomics medicine will diminish rather than enhance existing sex-, race-, and socioeconomic class-based inequities in health care access and delivery. This article describes some but not all aspects of the ethical, legal, and social implications of genomics in clinical practice.
Genetics, Medical↗
Autoimmune chronic pancreatitis: a plea for simplification and consistency.
Explore the source record for details and available documents.
Alkaline Phosphatase↗
Rapid endoscopic secretin stimulation test and discrimination of chronic pancreatitis and pancreatic cancer from disease controls.
BACKGROUND & AIMS: The cholecystokinin (CCK)/secretin pancreatic function tests to diagnose pancreatic exocrine insufficiency are time consuming and invasive. Our aim was to develop a rapid pancreatic function test performed during upper endoscopy that could discriminate between patients with normal from impaired exocrine pancreatic secretion. METHODS: We prospectively evaluated 412 patients for possible pancreatic diseases. During upper endoscopy, 1 CU/kg of secretin was given intravenously and duodenal juice (collected for 10 min) was assayed for concentrations of bicarbonate and lipolytic and trypsin activity. Final diagnosis was by histology, imaging, and a previously validated scoring system (for chronic pancreatitis). Of 412 patients, 117 patients had normal pancreas, 72 patients had chronic pancreatitis, and 116 patients had pancreatic adenocarcinoma. The remaining 107 patients had miscellaneous disease of the peripancreatic region. In 28 patients we also validated the secretin test with the standard CCK pancreatic function test. RESULTS: There was no difference between bicarbonate or trypsin concentrations among the groups. Lipolytic concentration was significantly lower in chronic pancreatitis (115 +/- 18) and in pancreatic adenocarcinoma (87 +/- 10) compared with patients with normal pancreas (229 +/- 23; P < 0.03 and P < 0.0001, respectively). The overall accuracy of the endoscopic secretin test was 79%, with positive and negative predictive values of 73% and 85%, respectively. The concentration of lipolytic activity obtained by the endoscopic secretin test in 28 patients correlated moderately well (r = 0.41, P < 0.03) with lipolytic output obtained by the CCK pancreatic function test. CONCLUSIONS: Lipolytic concentration in duodenal juice after intravenous secretin collected for 10 minutes during upper endoscopy was significantly lower in chronic pancreatitis and pancreatic adenocarcinoma compared with patients with normal pancreas, but was not accurate enough for routine clinical use.
Adenocarcinoma↗
Effect of triglyceride structure on fecal excretion of 13C-labeled triglycerides.
OBJECTIVE: The aim of this work was to determine the effects of specific changes in the structure of (13)C-labeled triglyceride (TG*) on its fecal excretion relative to total stool fat excretion determined simultaneously in patients with reduced exocrine pancreatic function. METHODS: A series of 47 studies were conducted in 26 young cystic fibrosis (CF) patients and 11 adult patients with chronic pancreatitis over a five year period. Each test consisted of ingesting a single high fat test meal containing both (13)C-labeled triglyceride (TG*) and dysprosium chloride (DyCl(3)) a nonabsorbable marker of intestinal transit; in most studies the food colorant brilliant blue (FD&C blue #1) was administered along with the DyCl(3). The TG*s tested were: P*P*P* = TRIPALMITIN-1,1,1-(13)C(3); SO*S = 2-OCTANOYL-1,3-DISTEARIN-2-octanoyl-1,2-(13)C(2); and P*LP* = 2-LAURYL-1,3-DIPALMITIN-dipalmitoyl-1,1,2,2-(13)C(4). Ingestion of the test meal was followed by collection of individual stools for at least 72 hours. Stools were analyzed for (13)C-Excess ((13)C*), total fat, and Dy. RESULTS: Excretion of P*LP* showed a high degree of linear correlation with stool fat (r(2) = 0.924) over a wide-range of fecal fat values. Excretion of SO*S was also significantly correlated with stool fat, but its excretion was less than 10% at all levels of steatorrhea and the slope of the regression line relating TG* excretion to stool fat was some four to five times smaller than observed for P*LP*. Fecal excretion of P*P*P* was highly correlated with stool fat (r(2) = 0.941) in patients with moderate steatorrhea (<25 g fat/24 hours) and the slope of the regression line (3.20) was considerably greater than for P*LP*. Only results from those studies in which stool collections were complete (Dy excretion >90%) were utilized in the statistical comparisons (36 of 47 studies). CONCLUSIONS: The observed highly significant linear correlation between P*LP* and stool fat over the entire range of steatorrhea suggests that P*LP* excretion may be a suitable surrogate for fecal fat in patients with reduced exocrine pancreatic function. Because fecal excretion of TG* administered as described can be accurately determined by sampling only two visually marked stools, development of a noninvasive test to replace the current 72-hour stool fat test using this approach is possible. Use of other engineered TG*s and/or labeled fatty acids, may provide a method for non-invasive in vivo assessment of the specific defect(s) leading to steatorrhea in other patient groups.
Adolescent↗
Chronic pancreatitis.
PURPOSE OF REVIEW: We are beginning to better understand the causes of chronic pancreatitis. This knowledge will hopefully lead to better diagnosis and treatment and abandonment of ill-conceived treatments. This review highlights contributions that moved the field toward these goals in the past year. RECENT FINDINGS: Small steps have been made toward a better understanding of the molecular basis, particularly genetic causes, of the forms of chronic pancreatitis. Investigation of the role of stellate cells, an essential component of the fibrosis of chronic pancreatitis, has led to the finding that lovastatin inhibits stellate cell activation and could surface as a novel treatment of chronic pancreatitis. The clinical description of autoimmune pancreatitis has led to the realization that steroids are effective treatment for this form of chronic pancreatitis. Other treatments such as extracorporeal shock wave lithotripsy and endoscopic treatments have not been proved, because no controlled studies support these treatments over other treatments. The diagnosis of chronic pancreatitis may be enhanced by the new imaging technique of electronic pancreatoscopy whereby a 2.1-mm diameter scope can be advanced into the pancreatic duct through a duodenoscope. However, the data are too preliminary at this time to advocate this imaging procedure. A potential new endoscopic pancreatic function test may lead to more widespread use of function testing, but this test is not perfected and also cannot be advised for use at present. SUMMARY: Ongoing basic and clinical research this past year has further characterized the genetic, molecular, and clinical aspects of chronic pancreatitis: efforts that may translate into novel therapies, once well-designed, controlled studies have been performed.
Journal Article↗
Intraductal papillary mucinous neoplasm: did it exist prior to 1980?
INTRODUCTION: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas was first reported in 1982. It is not clear whether the appearance of this neoplasm is a new epidemic or an old disease previously overlooked. AIM: To determine whether IPMN existed as a separate entity before 1982. METHODOLOGY: We reviewed our pathology reports from all cases of pancreatic cancer diagnosed between 1960 and 1980. Pathologic specimens with descriptors--"mucinous," "cystic," or "papillary"--underwent histologic reexamination. Medical records for patients given a new diagnosis of IPMN from this pathologic review were assessed. RESULTS: Eighty-four of more than 4,000 pathology reports reviewed contained a key word triggering histologic review. IPMN was identified in 21 patients. Patients had a mean age of 63 years (range, 44-77 years) with symptoms present for a mean of 76 months (median, 15 months; range, 1-516 months). Reported symptoms were abdominal pain in 17, jaundice in 13, weight loss in 12, and pancreatic insufficiency in 7 patients. On pathologic review, the in situ component was graded as adenoma in 4, borderline in 4, and carcinoma in 13. Parenchymal invasion was present in 11/21 (52%). Excluding four postoperative mortalities, mean time to death was 58 months (median, 15 months; range, 2-264 months). Seven patients died of IPMN, 4 of other causes without evidence of recurrence, and 6 of unknown causes. CONCLUSIONS: IPMN existed in its current known form prior to 1982. Our study cannot determine whether the prevalence or incidence has changed since that time.
Adenocarcinoma, Mucinous↗
Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas.
BACKGROUND & AIMS: The aim of this study was to determine recurrence and long-term survival after resection of pancreatic intraductal papillary mucinous neoplasm and to correlate recurrence and survival with histology, extent of resection, and duration of follow-up. METHODS: A single pathologist, without knowledge of previous interpretations of histology or clinical data, retrospectively reviewed and classified 113 resected intraductal papillary mucinous neoplasms as invasive carcinoma (n = 40) or as noninvasive neoplasms (adenoma, borderline, or carcinoma in situ; n = 73). Data on recurrence (locoregional or metastatic), follow-up, and cause of death were obtained from patient records and/or by contacting patients and their physicians. RESULTS: In invasive intraductal papillary mucinous neoplasm, recurrence was similar after partial pancreatectomy (18/27; 67%) and total pancreatectomy (8/13; 62%) and occurred within 3 years of resection in 91%. Among noninvasive neoplasms, 5 of 60 (8%) recurred after partial pancreatectomy (median follow-up, 37 months); none recurred after total pancreatectomy (n = 13; median follow-up, 32 months). Recurrence after resection in noninvasive neoplasms was diagnosed after a median of 40 months (range, 23-75 months); recurrence was noninvasive in 3 and invasive cancer in 2. Five-year survival was better for noninvasive compared with invasive intraductal papillary mucinous neoplasm (84.5% vs. 36%; P < 0.001). CONCLUSIONS: Invasive intraductal papillary mucinous neoplasm recurs frequently even after a complete "curative" resection and portends poor survival. In contrast, noninvasive intraductal papillary mucinous neoplasm recurs infrequently after resection, and survival is excellent regardless of the degree of epithelial dysplasia in the tumor.
Adenocarcinoma, Mucinous↗
Invasive cancer and survival of intraductal papillary mucinous tumors of the pancreas.
OBJECTIVES: Intraductal papillary mucinous tumor (IPMT) is frequently associated with pancreatic cancer. We hypothesized that IPMT progresses to invasive cancer with K-ras mutations as an early event, and that invasive cancer affects survival. We compared survival after resection and determined whether K-ras mutations predicted survival in IPMT patients without or with invasive cancer. METHODS: Records of 47 patients with IPMT who were seen between 1983 and 1998 were reviewed retrospectively in 15 cases and prospectively in 32. All histological material was reviewed to confirm the diagnosis of IPMT and to assess invasion. Kaplan-Meier survival curves were analyzed by the log-rank test. The chi2 test was used for differences in K-ras between groups. RESULTS: There were 30 men and 17 women, with a mean age of 65 yr (range 36-90 yr). Of the patients, 26 had IPMT without invasive cancer and 19 had IPMT with invasion. Tissue diagnosis was available in 45 patients. K-ras was analyzed in 40 patients. Mutations were present in 15 of 23 patients (65%) without invasive cancer and in 14 of 17 patients (82%) with invasive cancer (p = ns). At 2.5 yr, the overall cumulative survival of IPMT patients without invasive cancer was 94% compared to 24% of patients with invasive cancer (p < 0.001). The 5-yr survival of IPMT patients without invasive cancer was 94%. K-ras mutations did not correlate with survival. CONCLUSIONS: Invasive cancer in IPMT reduces the 2.5-yr survival after surgery from 93% to 24%. K-ras mutations occur before invasive cancer, and do not predict postoperative survival.
Adult↗