Diagnosis Of Pancreatic Carcinoma Research Articles

Radiologic Diagnosis and Staging of Pancreatic Ductal Adenocarcinoma

IBD CT is the single best modality for diagnosis and staging of patients with suspected pancreatic carcinoma. While carefully performed real-time US is an excellent technique for determining the level and etiology of bile duct obstruction, it is of more limited value for diagnosis of tumors in the body and tail of the gland, and is less accurate than IBD CT for assessment of tumor resectability. Thus, most patients require IBD CT for accurate, nonoperative staging. ERCP and angiography continue to be useful adjunctive procedures for evaluation of patients with suspected pancreatic carcinoma, particularly for evaluation of equivocal CT or US findings. An isolated pancreatic mass, that is, a mass with no ancillary CT or US findings of carcinoma (local extension, distant metastases), is a non-specific finding and requires further evaluation with either ERCP or angiography, and perhaps most importantly, with FNAB. Other neoplasms may mimic pancreatic ductal carcinoma, particularly islet cell carcinoma and lymphoma. Pancreatitis also can result in a focal pancreatic mass, simulating a neoplasm. These diseases usually respond to therapy and thus it is essential to confirm the radiologic diagnosis of pancreatic carcinoma with biopsy, particularly if surgery is not planned or if chemoradiation therapy is anticipated.

Immunohistochemical localization of CA 19-9 and CEA in pancreatic carcinoma and associated diseases.

The distribution of carbohydrate antigen 19-9 (CA 19-9), on pancreatic carcinomas and associated diseases correlated with carcinoembryonic antigen (CEA) localization is described. Immunohistochemical examinations were made on pancreatic specimens from 45 patients with pancreatic carcinoma. In normal pancreatic duct, the antigens were restricted to the luminal surface. In some hyperplastic epithelium, however, they were localized not only to the basolateral plasma membranes but also to the cytoplasm. In neoplastic glands, the antigens were distributed over the entire surface of the cells and in the surrounding stroma adjacent to the basal membranes of the malignant cells. The findings were compatible with previous observations of CEA and secretory component (SC) localization in gastric and colonic mucosa. In addition, the staining intensity of CA 19-9 in the routine formalin-fixed and paraffin-embedded sections was much superior to that of CEA. The relationship between CA 19-9 and other blood group antigens, such as Lewis a and Lewis b, also was discussed. Localizations of these antigens in pancreatic tissues are useful for the biologic analysis of abnormalities of the pancreatic duct epithelium, and may well facilitate pathologic diagnosis of pancreatic carcinoma.

Treatment of probable subclinical liver metastases and gross pancreatic carcinoma with hepatic artery 5-fluorouracil infusion and radiation therapy.

Since subclinical hepatic metastases are frequently present at time of diagnosis of pancreatic carcinoma, any meaningful effort to improve survival must include 'prophylactic' liver therapy in addition to treatment of the pancreatic primary. We report the results of a prospective, unrandomized clinical trial of a 2-week liver and pancreas infusion (by hepatic artery) of 5-fluorouracil (5-FU) and pancreatic irradiation to 50-60 Gy, combined with prophylactic irradiation of the liver with approximately 20 Gy. Of 21 evaluable patients, 17 completed therapy without excessive toxicity and had a median survival of 50 weeks. Contrary to historical controls, the liver in our series was rarely the first site of failure (6%), suggesting that the combination of hepatic artery 5-fluorouracil and 20 Gy liver radiation may suppress subclinical (microscopic) liver metastases without significant hepato-toxicity. When radiation doses to the pancreas were increased above 50 Gy there was improvement in primary tumor control, although failure in the pancreatic bed remained the most common site of failure. Future clinical investigation of this form of combined therapy for eradication of micro-metastasis in the liver, combined with more aggressive local pancreatic therapy, would seem appropriate.

Low serum testosterone/dihydrotestosterone ratio in patients with pancreatic carcinoma.

Serum testosterone, its metabolite 5 alpha-dihydrotestosterone, and the testosterone/dihydrotestosterone ratio were investigated in 22 male patients with proven pancreatic cancer, and compared with values from male patients with chronic pancreatitis (n = 21) and with nonpancreatic gastrointestinal tumors (n = 19). Testosterone and the testosterone/dihydrotestosterone ratio were significantly lower (p less than 0.001) in the pancreatic cancer group when they were compared with the other two groups. There was no significant difference in the dihydrotestosterone values between cancer groups. A testosterone/dihydrotestosterone ratio of less than 5 clearly distinguished most of the patients (20/22) with cancer of the pancreas from those with other tumors or chronic pancreatitis. The results suggest an alteration in the serum androgen profile in these patients. Therefore, the testosterone/dihydrotestosterone ratio could be a useful marker in the diagnosis of pancreatic carcinoma in male patients.

Percutaneous fine-needle aspiration biopsy of the pancreas.

Percutaneous fine needle aspiration biopsy of the pancreas allows to obtain without surgery a tissue proven diagnosis of focal lesions of the pancreas. Ultrasound (US), computed tomography (CT), or fluoroscopy are used to guide the positioning of the needle in the lesion. Various benign and malignant lesions can be diagnosed and the cytologic features of them are presented. The average sensitivity of the technique in the diagnosis of pancreatic carcinoma is 80.5% in the literature. The use of percutaneous fine needle biopsy of the pancreas decreases the number of investigations to be done in a patient with pancreatic disease.

Abnormal insulin secretion in carcinoma of the pancreas: response to glucagon stimulation.

In 34 patients suspected of having pancreatic cancer glucose homeostasis and insulin secretion in response to intravenous glucagon (1 mg) were studied prospectively. Twelve patients had pancreatic cancer at laparotomy and the remainder were designated a control group. Responses were also measured in 12 healthy volunteers. There was no significant difference in the rise of blood glucose between the groups after glucagon. The mean plasma insulin concentrations rose rapidly in both groups after glucagon but were significantly lower in the pancreatic cancer group. In patients with obstructive jaundice the plasma insulin response was a better discriminator of pancreatic cancer. Abnormal pancreatic beta-cell function is detectable in patients with pancreatic carcinoma before any change in glucose homeostasis, particularly in patients with obstructive jaundice. The glucagon stimulation test may be useful in the earlier diagnosis of pancreatic carcinoma before the development of clinically overt diabetes mellitus.

Serum ribonuclease in the diagnosis of pancreatic carcinoma and in monitoring chemotherapy.

Although serum ribonuclease (RNAase) activity (measured by Reddi's method [1]) was significantly higher in 24 patients with pancreatic carcinoma (mean 12.5 units) than in 93 control subjects (mean 5.0 units), 14 patients with chronic pancreatitis (mean 5.2 units) and 83 patients with other primary malignancies (mean 6.8 units), there was much overlap between the four groups and considerable (16.5%) inter-assay variation. Modification of the assay to eliminate a substrate inhibition effect gave acceptable inter-assay variation but abolished any significant difference between the four groups. Changes in serum RNAase activity did not reflect clinical changes in patients with pancreatic carcinoma followed serially during a trial of chemotherapy. The results indicate that serum RNAase is not a useful marker of pancreatic carcinoma.

Radiology in Disorders of the Liver, Biliary Tract and Pancreas: With Special Reference to the Use of Angiography in the Diagnosis of Resectable Tumors

This beautiful radiological atlas illustrates modern diagnostic concepts that are used in the evaluation of hepatobiliary and pancreatic diseases. Tumor screening, done by scintigraphy, ultrasound, and computed tomography, is followed by a combination of percutaneous transhepatic cholangiography (PTC), endoscopic retrograde cholangiopancreatography (ERCP), and high-quality visceral angiography for more definitive diagnosis and staging. From his extensive experience with pancreatic biliary disease, Dr Ariyama reports an unusually high degree of success (over 90%) with retrograde cannulation of the bile duct and the pancreatic duct, all without morbidity, a remarkable feat of technical wizardry. Unfortunately, clinical and technical details are not described in the text, but most can be found from the bibliography. Useful diagnostic information is given in the presentation of large series of hepatomas and biliary tract malignancies. Ariyama has made an important contribution in the early diagnosis of pancreatic carcinoma by championing the free and early use of ERCP and

Pancreatic arteriography, transhepatic pancreatic venography, and pancreatic venous sampling in diagnosis of pancreatic cancer.

Arteriography with visualization of small intrapancreatic arteries is a sensitive method in the diagnosis of pancreatic carcinoma. It can detect small intrapancreatic tumors and differentiate neoplasms from other pancreatic lesions. It also aids in staging pancreatic cancer and determining resectability. Transhepatic pancreatic venography is less sensitive than arteriography but it also can be useful in evaluating tumor operability. Pancreatic venous sampling is an important method for localizing hormone-secreting islet cell tumors.

Standard radiologic diagnosis and CT scanning in pancreatic cancer.

Routine radiography plays little role in the current diagnosis of pancreatic carcinoma, though some studies may be of use in treatment planning for specific patients. CT scanning is an important tool in the diagnosis of symptomatic pancreatic carcinoma. With present technology it is not a survey technique because lesions that do not deform the pancreatic contour are generally missed. Development of more sophisticated scanners or pancreatic-specific x-ray dyes may change this. At present, CT should be used in diagnosis and treatment planning for symptomatic patients either in conjunction with other tests or as the primary diagnostic procedure, depending upon the problems presented by the individual patient.

Cytologic studies for the diagnosis of pancreatic cancer

Endoscopically obtained fluid from the ampulla of Vater was subjected to cytologic examination in 141 of 159 patients with suspected pancreatic disease, most of whom were undergoing endoscopic retrograde cholangiopancreatography (ERCP) examination. Of 26 patients with proven carcinoma of the pancreas, cannulation of the ampulla was successful in 22, and in 12 of these the cytology was positive (54%). Several technical considerations are suggested to increase the yield of positive cytology. They include aspiration of 3 ml or greater, deep insertion of the cannula, collection of pure pancreatic juice, high suction, and use of a fine intraductal rasp. The diagnostic sensitivity of ERCP alone was 73% in patients with cancer, but in combination with cytology it increased to 85%. The combined evaluation yielded 100% accuracy in 22 cases of cancer in which the ampulla was successfully cannulated. In 51 patients with chronic pancreatitis, and in 75 without proven pancreatic disease, the specificity of cytology was 98% and 97% respectively. The specificity of ERCP in chronic pancreatitis was 94%. Cytology is a useful adjunct to the ERCP examination in the diagnosis of pancreatic carcinoma.

Frozen section diagnosis of pancreatic carcinoma: a prospective study of 64 biopsies.

Useful morphologic criteria for frozen section diagnosis of pancreatic and periampullary carcinoma were established by prospective review of 64 frozen sections in this region, with permanent section correlation and patient follow-up. These were divided into three major and five minor criteria based on frequency of occurrence and reproducibility. Major criteria were: 1) nuclear size variation of 4:1 or greater between ductal epithelial cells, 2) incomplete ductal lumens, and 3) disorganized duct distribution. Minor criteria, less frequently and reproducibly observed but valuable diagnostic aids, included: 1) huge, irregular epithelial nucleoli; 2) necrotic glandular debris; 3) glandular mitoses; 4) glands unaccompanied by connective tissue stroma within smooth muscle bundles (periampullary biopsies); and 5) perineural invasion. Combined application of both major and minor criteria is especially helpful in cases complicated by chronic pancreatitis.

The computer tomographic appearances of carcinoma of the pancreas (author's transl)

The computer tomographic appearances of carcinoma of the pancreas as seen in 75 patients are described. This radiological method provides conclusive diagnostic information; differential diagnostic aspects in the diagnosis of pancreatic carcinomas are discussed.

Sensitivity and specificity of serum ribonuclease in the diagnosis of pancreatic cancer

The serum levels of a poly-[C]-specific acid ribonuclease (RNase) found in the pancreas was measured in 40 normal persons and 137 patients with pancreatic cancer, other cancers, obstructive jaundice, acute pancreatitis or chronic pancreatitis. Serum RNase increased by as much as 800 percent above normal in 69 percent of patients with pancreatic cancer. Analysis of the serum isoenzymes of RNase by isoelectric focusing did not reveal any unique RNases produced by the tumors. In contrast, serum RNase rose in only 8 percent of patients with other cancers, 11 percent of other patients with obstructive jaundice and in no patients with chronic pancreatitis. These data suggest that the finding of increased serum RNase is of adjunctive value in the diagnosis of pancreatic carcinoma and may be particularly helpful in distinguishing it from other causes of biliary obstruction and from chronic pancreatitis.

Serum RNase in the diagnosis of pancreatic carcinoma.

Serum RNase (RNase I; ribonuclease 3'-pyrimidino-oligonucleotidohydrolase, EC 3.1.4.22) activity (mean +/- SD) with polycytidine as substrate was determined in normal individuals (24.9 +/- 3.0 units/ml) and in patients with pancreatic cancer (37.3 +/- 14.8), pancreatitis (38.5 +/- 12.6), nonpancreatic diseases (48.7 +/- 14.8), or renal failure (175.8 +/- 92.8). Patients with pancreatic cancer could not be distinguished from those with pancreatitis or with nonpancreatic disease, although the RNase activities in all of these differed from the activity in normal individuals. The serum RNase activities of four patients with resectable "curable") pancreatic carcinoma and two others with advanced pancreatic cancer without obstructive jaundice were normal. After total pancreatectomy, serum RNase activity remained in the high-normal range. The data presented here and data in the literature show that serum RNase cannot be of primarily pancreatic origin. The present study also demonstrates that measurement of its activity is not useful in early detection of pancreatic cancer.

Computerized tomography, diagnostic ultrasound, and radionuclide scanning: comparison of efficacy in diagnosis of pancreatic carcinoma: Barkin J, Vining D, Miale A Jr, Gottlieb S, Redlhammer DE, Kaiser MH, JAMA 239:2040, 1977

Computerized tomography, diagnostic ultrasound, and radionuclide scanning: comparison of efficacy in diagnosis of pancreatic carcinoma: Barkin J, Vining D, Miale A Jr, Gottlieb S, Redlhammer DE, Kaiser MH, JAMA 239:2040, 1977

Rapid diagnosis of pancreatic carcinoma.

An algorithmic approach for radiological evaluation of suspected pancreatic carcinoma was applied in more than 200 patients. Outpatient ultrasonography and barium studies of the upper gastrointestinal tract were followed by inpatient endoscopic retrograde cholangiopancreatography, angiography, and percutaneous biopsy. Evaluation took no more than two hospital days and exploratory laparotomy was not needed. Twenty-five patients had carcinoma. The diagnostic accuracy of the algorithm was 96%. Although this method did not increase the diagnosis of resectable tumors, it did result in rapid, accurate diagnosis of pancreatic carcinoma at relatively low cost and with minimum patient discomfort. Hopefully, these results will eventually lead to earlier diagnosis and improved survival.

Evaluation of endoscopic retrograde cholangiopancreatography and angiography in the diagnosis of pancreatic carcinoma

A series of 118 patients with suspected pancreatic disease was studied by endoscopic retrograde cholangiopancreatography (ERCP). Angiography was subsequently performed in 30 of these patients. ERCP was 95% accurate in the prospective diagnosis of pancreatic carcinoma. This study suggests that angiography is valuable in determining tumor resectability following ERCP diagnosis of pancreatic carcinoma. Angiography may obviate the need for exploratory laparotomy in patients with unresectable tumors and encourage aggressive treatment of resectable lesions. Patients with a high clinical suspicion of pancreatic disease should have angiography if the ERCP is normal, equivocal, or there is a cannulation failure.

Ultrasonic Sounds and Pancreatic Carcinoma-Reply

In Reply.— The intent of our study was to show that diagnosis of pancreatic carcinoma by ultrasonic scanning, like all other diagnostic techniques reported, has no effect on survival. However, ultrasonic scanning was remarkably reliable (abnormal in 24 of 28 patients) in providing a diagnosis. Ultrasonic scanning is considered to be safe, simple, and quite worthwhile. It continues to be the initial study of choice in our institution for patients suspected of having pancreatic cancer, before resorting to computerized tomographic (CT) scanning. Although it may not yet be proved that CT scanning will be more sensitive than ultrasonic scanning in diagnosing pancreatic malignant neoplasms, this is very likely to occur. However, it is somewhat less certain that CT scanning will be able to alter the survival of these patients any more than any other presently available technology. It also remains to be seen whether new programs of chemotherapy and radiotherapy

Preoperative diagnosis of pancreatic carcinoma by percutaneous aspiration biopsy

Carcinoma of the pancreas and chronic pancreatitis may be extremely difficult to differentiate by standard diagnostic methods preoperatively as well as at the operating table. Operative pancreatic biopsy may have a high morbidity, rare mortality, and can be misleading. Percutaneous aspiration biopsy may be of great potential benefit. It provides additional histological material not usually available, and an accurate diagnosis of malignancy can be made. In select patients a needless laparotomy may be avoided. It appears to be a safe procedure that should be considered in the evaluation of the patient with suspected pancreatic malignancy in which a mass lesion is demonstrated by ultrasonography, computerized tomography, angiography, or retrograde pancreatography.