Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An acinar cell carcinoma of the pancreas, which developed in a F-344 rat after long-term nafenopin administration, was serially transplanted into inbred weanling rats by subcutaneous and intraperitoneal routes. The transplantability rate was 95% or more by both routes. The tumor implants became palpable in 20 to 30 days after subcutaneous transplantation, increasing in size rapidly thereafter during the next 25 to 30 days. In intraperitoneal recipients the abdomen was markedly distended within 1 month. No metastases were observed in this series of transplantations. Amylase and lipase levels in serum and tumor homogenates increased with tumor size. Morphologically, only a few cells contained zymogen granules immediately after the appearance of a palpable tumor; at later intervals, however, these granules were observed in many tumor cells. Seventy-two hours after the surgical removal of tumors, the serum amylase and lipase levels returned to control values. This transplantable pancreatic acinar cell carcinoma can be dissociated into functionally viable single cells by a simplified enzyme digestion and divalent cation chelation procedure. By light microscopic autoradiography, approximately 20% of these isolated cells were found to incorporate (3)H-thymidine in vitro into nuclear DNA. The data presented in this paper should serve as a baseline for future studies on this transplanted tumor.
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PMID:Transplantable acinar cell carcinoma of the rat pancreas. 42 31

We have examined the microscopic appearance, immunohistochemical staining properties, and clinical behavior of 28 cases of acinar cell carcinoma of the pancreas. Two of the tumors occurred in children. The adult patients ranged in age from 40 to 81 years (mean, 62 years). Males greatly outnumbered females, and most of the patients were white. Presenting symptoms were nonspecific, and jaundice was infrequent. The frequently reported complications from increased serum lipase levels (i.e., arthralgias and subcutaneous fat necrosis) were present in only 16% of the patients. Grossly, the tumors were relatively circumscribed and fleshy, averaging 10.8 cm, with occasionally extensive hemorrhage and necrosis. Microscopically, the tumors were very cellular and characteristically lacked a desmoplastic stroma. Acinar, solid, trabecular, and glandular patterns of growth were identified; individual tumors were usually mixed. Nuclei were round to oval, with minimal pleomorphism and single prominent nucleoli. Mitotic activity was variable. In general the cytoplasm was moderately abundant, eosinophilic, and granular, but many of the solid tumors had cells with scanty cytoplasm. Characteristic periodic acid-Schiff-positive, diastase-resistant cytoplasmic granules were demonstrated in greater than 90% of the cases, and the butyrate esterase histochemical stain for lipase activity was positive in 73%. Immunohistochemically, there was positivity for trypsin in 100% of the cases, for lipase in 77%, for chymotrypsin in 38%, and for amylase in 31%. A minor endocrine component was recognized with antibodies against chromogranin or islet cell hormones in 42% of the tumors. Ultrastructurally, exocrine secretory features were present, with polarized cells showing microvillilined lumina, abundant rough endoplasmic reticulum, and 125-1,000-nm zymogen-like granules. In addition, many cases showed pleomorphic electron-dense granules measuring up to 3,500 nm and containing fibrillary internal structures. Follow-up information was available in 88% of the cases. Half of the patients had metastatic disease at presentation and an additional 23% subsequently developed metastases, which were usually restricted to the regional lymph nodes and liver. The mean survival for all cases was 18 months, with 1- and 3-year survivals of 57 and 26%, respectively. Patients presenting before age 60 years survived nearly twice as long as older patients did. Stage also influenced prognosis, whereas the histologic subtype of the tumors and the location within the pancreas correlated only weakly with survival.
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PMID:Acinar cell carcinoma of the pancreas. A clinicopathologic study of 28 cases. 138 74

A 46 year old white man presented with subcutaneous and intramedullary fat necrosis, destructive polyarthritis, and osteolytic bone lesions, complicating a poorly differentiated adenocarcinoma of the tail of the pancreas with metastases in the liver and omentum. There was a 100-fold increase in serum lipase and trypsin activity. His condition deteriorated rapidly, was characterised by rapid tumour growth, formation of ascites, a 20 kg weight loss, extensive subcutaneous fat necrosis, and fistula formation in the left calf. Treatment with 5-fluorouracil 300 mg/m2 on days 1-5 and doxorubicin 50 mg/m2 and cisplatin 100 mg/m2 on day 1, every three weeks, was well tolerated and resulted in rapid clinical improvement. After three courses of treatment a partial remission was seen and after seven courses further improvement occurred with a return to normal of serum lipase and trypsin activity. One year after starting chemotherapy the tumour relapsed but responded again to chemotherapy (epirubicin 40 mg/m2 and carboplatin 300 mg/m2 on day 1, every three weeks).
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PMID:Pancreatic carcinoma with polyarthritis, fat necrosis, and high serum lipase and trypsin activity. 238 23

The synthetic dithiolethione Oltipraz has marked cancer chemopreventive and phase II enzyme inducing activity in various animal carcinogenesis models, but has not been examined in any animal models of ductal pancreatic cancer relevant to the human disease. The chemopreventive potential of Oltipraz on pancreatic tumor incidence and multiplicity was examined in the N-nitrosobis(2-oxopropyl)-amine (BOP)-induced ductal pancreatic adenocarcinoma model in Syrian hamsters. Animals were maintained on control semipurified diets or semipurified diets containing 300 and 600 mg/kg Oltipraz beginning 2 weeks prior to BOP initiation and throughout the 26 week study. Oltipraz at 300 mg/kg had no effect on the incidence or multiplicity of preneoplastic, neoplastic or metastatic lesions, while at 600 mg/kg dietary Oltipraz the incidence of pancreatic adenocarcinomas was reduced significantly (P < or = 0.05) compared to BOP-treated controls. Dietary Oltipraz at both doses had a significant influence on reducing mortality and morbidity in tumor-bearing animals with metastatic disease. At 26 weeks, total hepatic glutathione-S transferase (GST) activity and GST mu activity were elevated significantly in Oltipraz-treated animals, while total pancreatic GST activity was reduced, albeit not significantly. Serum lipase activity, a marker for pancreatic damage, exhibited a progressive decline in BOP-treated animals administered Oltipraz compared to BOP-treated controls at 12 weeks of the study; by week 26, lipase activity was comparable in all groups and reduced compared to activity at week 12. Positive nuclear immunostaining for the p53 tumor suppressor protein, a hallmark of human pancreatic cancer and a transient response to DNA damage, was observed in only a small percentage of BOP-induced pancreatic lesions and was not influenced Oltipraz administration. Further chemoprevention and pharmacologic studies of Oltipraz in relevant animal models of ductal pancreatic cancer could provide a foundation for future studies in human populations at potential risk for pancreatic cancer.
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PMID:Chemopreventive activity of Oltipraz against N-nitrosobis(2-oxopropyl)amine (BOP)-induced ductal pancreatic carcinoma development and effects on survival of Syrian golden hamsters. 755 69

Acinar cell carcinoma is a rare pancreatic neoplasm that may contain scattered endocrine cells in as many as 40% of cases. In addition, unusual tumors exist in which the acinar and endocrine components each constitute a significant proportion (> 25%) of the neoplasm; we propose to designate them as "mixed acinar-endocrine carcinomas." In a study of five such cases, we found one case with segregated areas of acinar and endocrine cells that were identifiable in routinely stained sections and four cases with morphologically uniform cell populations where the divergent differentiation was only detected immunohistochemically. The tumors occurred in adults (age range, 48-81; mean, 68); there were two men and three women. None of the patients presented with symptoms related to either enzyme or hormone liberation. Histologically, the tumors were very cellular; various combinations of solid, trabecular, acinar, and glandular growth patterns were noted. The cells contained d-PAS-positive granules and showed immunohistochemical positivity for pancreatic enzymes (trypsin, chymotrypsin, and lipase) and endocrine markers (chromogranin and synaptophysin); specific endocrine hormones were found in two cases. Double immunohistochemical staining for acinar and endocrine markers showed that most cells expressed only one line of differentiation. Ultrastructural study of two cases showed two populations of granules. Two of the patients died of their tumors (mean survival, 10.5 months), one with widespread metastases. Two patients were alive with disease at 12 months after diagnosis, and one patient was lost to follow-up after 3 months. This rare type of pancreatic neoplasm provides further evidence of the close histogenetic relationship between the exocrine and endocrine components of this organ.
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PMID:Mixed acinar-endocrine carcinomas of the pancreas. 803 90

A 51-year-old man developed a large retroperitoneal tumor with liver and lymph node metastases; there was no radiological evidence of pancreatic involvement. Despite the progression of disease, results of laboratory tests, notably serum amylase, were normal except for minor increases in aspartate aminotransferase and gamma-glutamyltransferase and a marked increase in lipase. The increased lipase was not attributable to formation of macroenzyme. To determine the source of the lipase, we fractionated serum and a tumor biopsy homogenate, using electrophoresis. The lipase pattern obtained from the patient's serum differed from that seen in serum from a patient with acute pancreatitis. Additionally, the lipase pattern obtained from a homogenate of biopsy sample from the retroperitoneal tumor did not match the pattern observed for normal pancreas. Apparently, the source of this increased serum lipase activity was the nonpancreatic tumor.
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PMID:Chronic increased serum lipase without evidence of pancreatitis: tumor-derived lipase? 859 14

A 33 years old woman presented with cramp-like abdominal pain. Ultrasound examination revealed multiple lesions in the liver of hyper- and hypoechoic echogenicity which in accordance to subsequently performed computed tomography and dynamic hepatobiliary scintigraphy were considered to be a focal nodular hyperplasia (FNH). A severe increase of the serum lipase concentration, suspected to be an acute pancreatitis, was treated conservatively and led to a short improvement of symptoms. Some months later, a severe progression of the pain symptoms occurred, along with a measurable expansion of the abdominal circumference and palpable tumors of the liver. The dynamic hepatobiliary imaging and the static liver scan showed a decreased perfusion and function of the nodes as well as a reduced RES activity, respectively. A subsequently performed Positron Emission Tomography (PET) with F-18-Fluorodeoxyglucose (FDG) showed a massively increased glucose metabolism of the liver tumors. The histologic result of several biopsies of the tumors revealed metastases of an acinus cell carcinoma of the pancreas. Under systemic and local chemotherapy, a temporary remission could be obtained that was clearly detectable in a second FDG-PET. Nevertheless, during the further course of the disease, a progression occurred being detectable in an additional control PET-study by an increase in tumor size as well as in tumor glucose metabolism. The patient died in liver coma 15 months after the histologic diagnosis was obtained.
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PMID:[Long-term follow-up and therapeutic control of a hepatic metastatic acinar cell carcinoma of the pancreas using FDG PET]. 972 47

Most exocrine pancreatic tumors are of ductal origin, whereas acinar cell adenocarcinomas are unusual (1% to 2% of all exocrine pancreatic neoplasms). We recently found a cystic adenocarcinoma of the pancreatic body whose cells had the characteristics of acinar cells, which we term acinar cell cystadenocarcinoma. Macroscopically, this tumor consists of a large multilocular cystic mass with a pseudocapsule and a spongy appearance on the cut surface. Microscopically, the cysts are lined by a single layer of cuboid/columnar cells. The cytoplasm has the characteristics of acinar cells, with eosinophilic granules in the apex and prominent nucleoli. Immunohistochemically, the cells express alpha1-antitrypsin, trypsin, and lipase in their cytoplasm, thus confirming the acinar origin of the tumor. A review of the literature revealed only 5 other cases of this tumor reported since its first description in 1981. Follow-up data are available for 4 of these; all of the affected patients had metastases at presentation or a few months later, and 2 died of the disease, at 13 and 37 months after diagnosis. Although this variant of adenocarcinoma of the pancreas is not prognostically different from the classic solid type (few patients survive more than 5 years), we believe that it is important because of its extreme rarity.
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PMID:Acinar cell cystadenocarcinoma of the pancreas: report of rare case and review of the literature. 1561 19

Composite tumors of the stomach consisting of mixed glandular and endocrine components are rare. We report 3 cases of composite glandular and endocrine tumors with pancreatic acinar differentiation in the stomach with their clinicopathologic findings. The patients' presenting symptoms were variable and included abdominal pain, gastrointestinal hemorrhage, and weight loss. One patient with abdominal pain also had an elevated serum lipase level, clinically mimicking acute pancreatitis. The histology of these tumors was similar. They showed admixture of well-differentiated endocrine components with acinar and glandular components. The glandular component consisted of columnar epithelial cells resembling gastric foveolar or intestinal goblet cells, consistent with a well-differentiated adenocarcinoma. A panel of histochemical and immunohistochemical stains was performed, which included PAS, Alcian blue, Mib1, CEA, cytokeratin 7, cytokeratin 20, Muc2, Muc5AC, chromogranin, synaptophysin, trypsin, chymotrypsin, lipase, insulin, gastrin, serotonin, and pancreatic polypeptide. While the immunoreactivity for cytokeratin 7, cytokeratin 20, Muc2, Muc5AC, and CEA was largely restricted to the glandular component, the endocrine and pancreatic acinar markers showed marked variability and overlap. All cases showed immunoreactivity for at least one of the exocrine pancreatic enzymes, and all expressed endocrine differentiation. Some degree of amphicrine differentiation was suggested in all cases. Two cases showed metastases in perigastric lymph nodes, which histologically resembled the primary tumor. In summary, these tumors represent another distinct type of composite glandular and endocrine gastric neoplasm with pancreatic acinar differentiation.
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PMID:Composite glandular and endocrine tumors of the stomach with pancreatic acinar differentiation. 1622 21

Pancreatic acinar cell carcinomas are rare, and little is reported on their chemotherapy. We report a 49-year old male patient with pancreatic acinar cell carcinoma and multiple liver metastases, which responded to oral TS-1 and hepatic arterial infusion of cisplatin. The patient underwent a partial hepatectomy, MCT abrasions and excision of the pancreatic tumor. Postoperative pathological studies revealed metastases of acinar cell carcinoma to the liver and lymph nodes; the primary lesion was undetermined. After surgery, the patient was treated with hepatic arterial infusion of cisplatin and oral TS-1. Metastatic tumors completely disappeared, and serum lipase decreased to normal levels. Abdominal CT one year after surgery revealed a pancreatic body tumor, which was surgically removed. Pathological studies showed primary pancreatic acinar cell carcinoma, while previous metastases remained under control. To summarize, TS-1 and cisplatin can be effective treatments for pancreatic acinar cell carcinomas.
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PMID:[Pancreatic acinar cell carcinoma successfully treated with combination of oral TS-1 and intra-arterial cisplatin]. 1661 67


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