Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More than 90% of tumours of the pancreas have mutations on codon 12 of the Ki-ras oncogene. Cellular DNA from pancreatic secretions and fine-needle biopsies, obtained from 69 patients (41 men, 28 women), were amplified by the polymerase chain reaction (PCR) to demonstrate this characteristic marker. All these patients had undergone endoscopic retrograde pancreatography for suspected pancreatitis or carcinoma of the pancreas. Two different methods were developed to demonstrate the mutations. With the aid of one of these methods, enrichment PCR with analysis of the restriction fragment length (FL), mutations on codon 12 of the Ki-ras gene were demonstrated in unstimulated pancreatic secretions of 29 of 33 patients with pancreatic carcinoma. All eleven fine-needle biopsies that had been cytologically examined showed the tumour-specific mutation. After direct sequencing of enrichment PCR a codon 12 mutation was demonstrated in pancreatic secretion from 21 of 24 patients and with the single strand conformation polymorphism analysis in 17 of 33 patients. In two of these 33 patients two different Ki-ras mutations were discovered. No mutations were found in acute inflammations or stone disease, while in five patients with chronic pancreatitis mutations were demonstrated only in those two patients in whom histological examination had revealed precancerous mucinous hyperplasia. This investigation indicates that codon 12 mutations of the Ki-ras gene, found after PCR in pancreatic secretion and biopsies, constitute a sensitive and specific tumour marker whose clinical value is being assessed.
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PMID:[Ki-ras mutation as a molecular tumor marker for carcinoma of the pancreas]. 778 24

The natural course of the classical symptoms of chronic pancreatitis, i.e. pain, exocrine and endocrine pancreatic insufficiency, was followed up in 335 patients over a median of 9.8 years (mean 11.3 +/- 8.3 years). Pain relief was not obtained in the majority of patients, even after a long-term observation of > 10 years, and severe exocrine/endocrine insufficiency, severe duct abnormalities and pancreatic calcifications developed. Alcohol abstinence failed to have a significant beneficial effect on pain. Pancreatic surgery led to pain relief immediately after operation, but later on the pain course between operated and nonoperated patients was not significantly different. Repeated exocrine pancreatic function tests in 143 patients showed that functional exocrine impairment came to a standstill (46%), or improved (11%). At the end of observation, 22% of 335 patients still had normal endocrine function and only 40% required insulin treatment. Alcohol abstinence had a significant beneficial effect on endocrine, but not on exocrine pancreatic insufficiency. Chronic pancreatitis led to a sharp increase in unemployment and retirement. Pancreatic carcinoma occurred in 3% and extrapancreatic carcinoma in 4%. The mortality rate within the observation period was 22%, pancreatitis-induced complications accounted for 13% of these deaths.
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PMID:Natural course in chronic pancreatitis. Pain, exocrine and endocrine pancreatic insufficiency and prognosis of the disease. 835 56

A patient with obstructive jaundice due to carcinoma of the pancreas head showed painless vomiting from the supra-papillary duodenal obstruction. Computed tomography demonstrated a space-occupying lesion in the head of the pancreas, which was not so large as to make an obstruction of the proximal portion of the duodenum. Pylorus preserving pancreatoduodenectomy was performed and the surgical specimen showed that the duodenal obstruction was caused by a swollen annular pancreas associated with obstructive pancreatitis by the carcinoma of the pancreas head. Duodenal obstruction is a rare symptom of annular pancreas in adults. It is thought to be necessary to remind of the coexistence of the annular pancreas, when patients with pancreatic or periampullary malignancies are complicated with unexpected obstruction of the second portion of the duodenum in proportion to the size.
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PMID:Duodenal obstruction due to annular pancreas associated with pancreatic head carcinoma. 884 13

Important advances in the understanding of pancreatic diseases have taken place through the application of molecular methods in the study of the inherited form of pancreatitis and pancreas cancer. Mutations of the cationic trypsinogen gene have been found to be causative for hereditary pancreatitis with important implications for the molecular pathogenesis of acute and chronic pancreatitis. A variety of cancer syndromes involving the P16 and BRCA2 genes, for example, also lead to pancreatic cancer, but the gene responsible for familial pancreatic cancer has not been identified so far. The establishment of a European Registry of Hereditary Pancreatitis and Pancreatic Cancer (EUROPAC) will facilitate future developments.
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PMID:Hereditary pancreatitis and familial pancreatic cancer. 943 3

Pancreata with cancer also frequently have intraductal proliferative lesions, suggesting an association between pancreatic cancer and these lesions. We present three cases in which atypical papillary hyperplasia of the pancreas was documented 17 months to 10 years before the development of an infiltrating adenocarcinoma of the pancreas. The first patient was a 70-year-old woman who underwent pancreaticoduodenectomy for adenocarcinoma of the pancreas. Atypical papillary duct hyperplasia extended to the pancreatic neck margin of resection, but the margin was negative for infiltrating carcinoma. Nine years later, an infiltrating adenocarcinoma developed in the remaining pancreas. The second patient was a 58-year-old man who underwent distal pancreatectomy for chronic pancreatitis with pseudocyst. Histologic examination showed chronic pancreatitis and multiple foci of atypical papillary duct hyperplasia. Ten years later, the patient underwent a Whipple procedure for infiltrating adenocarcinoma of the pancreas. The third patient was a 46-year-old woman with recurrent pancreatitis who underwent a Whipple procedure. Histologic examination showed atypical papillary duct hyperplasia and chronic pancreatitis but no infiltrating carcinoma. At the time of surgery, the tail of the pancreas was grossly and radiographically normal. Seventeen months later, a malignant pleural effusion developed, and postmortem examination showed infiltrating adenocarcinoma in the tail of the pancreas. In the cases presented, atypical papillary hyperplasia was documented 17 months, 9 years, and 10 years before the development of infiltrating adenocarcinoma of the pancreas, supporting the concept that there is a progression from intraductal hyperplasia to infiltrating carcinoma of the pancreas, just as there is a progression from adenoma to infiltrating carcinoma in the colorectum. Based on evidence that these intraductal lesions are precursor lesions to infiltrating adenocarcinoma of the pancreas, we suggest that the term "hyperplasia" be replaced by the more specific term "pancreatic intraepithelial neoplasia."
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PMID:Progression of pancreatic intraductal neoplasias to infiltrating adenocarcinoma of the pancreas. 950 Feb 16

Acute pancreatitis in cancer patients can be secondary to the malignant process itself or a complication of antineoplastic agent administration. However, acute pancreatitis caused by metastatic carcinoma of the pancreas is an uncommon condition with a poor prognosis. We report a case of a 63-year-old man with small cell carcinoma of the lung, who developed acute pancreatitis lately. Thirteen months earlier, he developed small cell carcinoma of the lung and received 6 cycles of chemotherapy. Abdominal CT scan showed swelling of the pancreas with multiple masses. The patient was managed conservatively and pancreatitis subsided. This case indicates that metastasis induced acute pancreatitis can be a manifestation of lung cancer, especially in small cell carcinoma.
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PMID:Metastasis-induced acute pancreatitis in a patient with small cell carcinoma of the lung. 1010 35

Pancreatic carcinoma is the fourth cause of death for cancer in the USA, carrying a dismal prognosis and poor overall survival. Unfortunately, resection for cure is feasible in a limited number of patients, thus confirming the need for an early diagnosis and accurate preoperative staging to select patients potentially resectable from those candidates to palliative treatment. Among imaging modalities, endoscopic procedures (endoscopic retrograde cholangiopancreatography, laparoscopy and endoscopic ultrasonography) play a key role in the diagnosis and staging of pancreatic tumors. Endoscopic retrograde cholangiopancreatography (ERCP) allows direct visualization of the main pancreatic duct and its side branches with their morphologic alterations, which are present in most cases of pancreatic cancer. The method is very sensitive in experienced hands, with diagnostic accuracy over 95%. The most common finding in pancreatic cancer is the stricture of the pancreatic duct, the bile duct, or both. Moreover, ductal brush cytology and K-ras mutation analysis can be performed during ERCP, possibly improving the diagnostic accuracy of the technique. Diagnostic laparoscopy provides detection of small (< 1 cm) liver metastases and peritoneal implants of tumor which cannot be visualized by any other imaging modality, with the possibility to biopsy under direct vision suspicious areas or to perform peritoneal lavage. The adjunct of laparoscopic ultrasound improves the staging capabilities of the technique for pancreatic cancer (retroperitoneal spread, vascular invasion). Endoscopic ultrasonography (EUS) is able to produce great detail of the pancreatic parenchyma and regional lymph nodes. It is especially sensitive in the detection of small pancreatic masses which cannot be imaged with other modalities. EUS has the additional advantage of directing transduodenal fine-needle aspiration biopsies. Presently it is the most sensitive technique for the diagnosis and locoregional staging of pancreatic cancer, but limits have been identified in the lack of specificity (differentiation between malignant tumor and focal pancreatitis) and its operator-dependency. Reported is our experience with EUS in the diagnosis and staging of pancreatic cancer. Over a seven-year period 43 patients with pancreatic tumors were staged with EUS preoperatively. Twenty-two patients were submitted to surgery at our Institution and EUS findings were compared with results of pathology or surgical exploration. EUS provided sensitivity of 100% for the diagnosis of pancreatic cancer, while its accuracy for staging tumor infiltration, lymph node involvement and vascular invasion was 86.4%, 69.2% and 77.8%, respectively. Despite improvements in the noninvasive imaging modalities, endoscopic techniques are likely to remain established methods for the diagnosis and staging of pancreatic cancer. EUS with fine-needle aspiration biopsy is probably the most promising, followed by laparoscopy (and laparoscopic ultrasound) which is essential to rule out small peritoneal implants and liver metastasis.
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PMID:[Endoscopy in the diagnosis and staging of pancreatic cancer]. 1023 74

Biliopancreatic malignancy is one of the leading causes of cancer death in the Western world. Defining at risk groups has been difficult. Diabetes mellitus and pancreatitis increase the risk of pancreatic carcinoma, and inflammatory bowel disease and associated sclerosing colangitis increase the risk of biliary tract malignancy. Pancreatic carcinoma has also been described in pedigrees with inherited cancer predisposition. Extensive molecular profiling of pancreatic carcinomas has been accomplished over the past few years, but similar knowledge in other biliopancreatic malignancies is lacking. In almost all pancreas cancers at least one alteration will occur out of a combination of K-ras mutations and inactivation of the tumor suppressor genes p16/MTS1/ink4a, p53 and DPC4/Smad4. Mutations of K-ras and p16 have been described in hyperplastic and dysplastic pancreatic ductal lesions believed to be the non-malignant precursors of pancreatic carcinoma. Detection of K-ras mutations in clinical samples (biliopancreatic secretions, stool, duodenal aspirates, and blood) identical to ones present in primary pancreatic cancers and/or their precursor ductal lesions has been reported in pilot studies. Recently detection of 18q deletions (at the DPC4 locus) in pancreatic secretions from early pancreatic cancers was also reported. These advances raise the possibility that within well defined at risk groups it will be possible to use a combined set of molecular markers to screen clinical samples and detect early pancreatic cancer or even pre-malignant lesions. The fulfillment of this promise will depend on proving the role of molecular screening in decreasing morbidity and mortality, which will require well designed clinical studies.
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PMID:Biliopancreatic malignancy: screening the at risk patient with molecular markers. 1043 11

The prevalence of pancreatic cancer in the general population is too low--even in high-prevalence areas such as Northern Europe and North America (8-12 per 10(5) population)--relative to the diagnostic accuracy of present detection methods to permit primary screening in the asymptomatic adult population. The recognition that the lifetime risk of developing pancreatic cancer for patients with hereditary pancreatitis (HP) is extremely high (20% by the age of 60 years and 40% by the age of 70 years) poses considerable challenges and opportunities for secondary screening in those patients without any clinical features of pancreatic cancer. Even for secondary screening, the detection of cancer at a biological stage that would be amenable to cure by surgery (total pancreatectomy) still requires diagnostic modalities with a very high sensitivity and specificity. Conventional radiological imaging methods such as endoluminal ultrasound and endoscopic retrograde pancreatography, which have proved to be valuable in the early detection of early neoplastic lesions in patients with familial pancreatic cancer, may well be applicable to patients with HP but only in those without gross morphological features of chronic pancreatitis (other than parenchymal atrophy). Unfortunately, most cases of HP also have associated gross features of chronic pancreatitis that are likely to seriously undermine the diagnostic value of these conventional imaging modalities. Pre-malignant molecular changes can be detected in the pancreatic juice of patients. Thus, the application of molecular screening in patients with HP is potentially the most powerful method of detection of early pancreatic cancer. Although mutant (mt) K-ras can be detected in the pancreatic juice of most patients with pancreatic cancer, it is also present in patients with non-inherited chronic pancreatitis who do not progress to pancreatic cancer (at least in the short to medium term), as well as increasingly in the older population without pancreatic disease. Nevertheless, the presence of mt-K-ras may identify a genuinely higher-risk group, enabling additional diagnostic imaging and molecular resources to be focussed on such a group. What is clear is that prospective multi-centre studies, such as that being pursued by the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC), are essential for the development of an effective secondary screening programme for these patients.
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PMID:Molecular diagnosis of early pancreatic ductal adenocarcinoma in high-risk patients. 1212 Feb 29

Recent observations suggest that an immune response is involved in the development of chronic pancreatitis. We report a case of autoimmune pancreatitis in a patient who showed complete obstruction of the lower common bile duct. A 63-year-old man was admitted to a local hospital, complaining of appetite loss and back pain. The patient had obstructive jaundice, and percutaneous transhepatic gallbladder drainage was performed. Fluorography through the biliary drainage catheter showed complete obstruction of the lower common bile duct. The patient had no history of alcohol consumption and no family history of pancreatic disease. Physical examination revealed an elastic hard mass palpable in the upper abdomen. Abdominal ultrasound and abdominal computed tomography (CT) scans showed enlargement of the pancreas head. While autoimmune pancreatitis was highly likely, due to the patient's high serum immunoglobulin level, the possibility of carcinoma of the pancreas and/or lower common bile duct could not be ruled out. Laparotomy was performed, and wedge biopsy samples from the pancreas head and body revealed severe chronic pancreatitis with infiltration of reactive lymphocytes, a finding which was compatible with autoimmune pancreatitis. Cholecystectomy and biliary reconstruction, using choledochojejunostomy, were performed, because the complete bile duct obstruction was considered to be irreversible, due to severe fibrosis. After the operation, prednisolone (30 mg/day) was given orally for 1 month, and the entire pancreas regressed to a normal size. Complete obstruction of the common bile duct caused by autoimmune pancreatitis has not been reported previously; this phenomenon provides an insight into autoimmune pancreatitis and provokes a controversy regarding whether biliary reconstruction is needed for the treatment of complete biliary obstruction caused by autoimmune pancreatitis.
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PMID:Complete obstruction of the lower common bile duct caused by autoimmune pancreatitis: is biliary reconstruction really necessary? 1575 5


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