Patrick J. Fitzgerald

Lymph node involvement in carcinoma of the head of the pancreas area.

A prospective study to determine the lymph node involvement in 33 pancreatectomy specimens (regional pancreatectomy 18, total pancreatectomy 7, Whipple partial pancreatectomy 8) was undertaken. There were 22 patients with pancreas duct adenocarcinoma, 6 with ampullary carcinoma, 3 with duodenal adenocarcinoma, 1 bile duct carcinoma and 1 of undetermined site of origin. Peripancreatic lymph nodes were divided into 5 main groups with subgroups. They are 1) Superior, Superior Head, Superior Body and Gastric; 2) Inferior: Inferior Head and Inferior Body, 3) Anterior: Anterior Pancreaticoduodenal, Pyloric and Mesenteric, 4) Posterior: Posterior Pancreaticoduodenal, Common Bile Duct, and 5) Splenic: lymph nodes at hilum of spleen and at the tail of pancreas. The average number of lymph nodes found in different types of surgical specimens was: regional pancreatectomy 70, total pancreatectomy 41, and Whipple procedure 33. The average number of lymph nodes involved with metastatic tumor in these specimens was, respectively, 5, 3 and 1. The most common sites of metastasis were in the Superior Head and in the Posterior Pancreaticoduodenal groups. Pancreatic duct adenocarcinoma tended to me‐tastasize to multiple lymph nodes of the Superior Head, Superior Body and Posterior Pancreaticoduodenal lymph nodes (88% of patients). Ampullary adenocarcinoma metastasized less often (33%), usually to fewer nodes and to one adjacent periampullary group. Since in 33% of patients nodal metastases of duct adenocarcinoma of the head of the pancreas were present in groups not usually removed in the Whipple procedure, it would appear that this operation is inadequate for surgical eradication of pancreas duct adenocarcinoma of the head of the pancreas.

Novel nonsecosteroidal vitamin D mimics exert VDR-modulating activities with less calcium mobilization than 1,25-dihydroxyvitamin D3

BACKGROUND The secosteroid 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) acts through the vitamin D receptor (VDR) to elicit many activities that make it a promising drug candidate for the treatment of a number of diseases, including cancer and psoriasis. Clinical use of 1,25(OH)2D3 has been limited by hypercalcemia elicited by pharmacologically effective doses. We hypothesized that structurally distinct, nonsecosteroidal mimics of 1,25(OH)2D3 might have different activity profiles from vitamin D analogs, and set out to discover such compounds by screening small-molecule libraries. RESULTS A bis-phenyl derivative was found to activate VDR in a transactivation screening assay. Additional related compounds were synthesized that mimicked various activities of 1,25(OH)2D3, including growth inhibition of cancer cells and keratinocytes, as well as induction of leukemic cell differentiation. In contrast to 1, 25(OH)2D3, these synthetic compounds did not demonstrate appreciable binding to serum vitamin D binding protein, a property that is correlated with fewer calcium effects in vivo. Two mimics tested in mice showed greater induction of a VDR target gene with less elevation of serum calcium than 1,25(OH)2D3. CONCLUSIONS These novel VDR modulators may have potential as therapeutics for cancer, leukemia and psoriasis with less calcium mobilization side effects than are associated with secosteroidal 1,25(OH)2D3 analogs.

The value of diagnostic aids in detecting pancreas cancer.

By contract with the National Cancer Institute, the accuracy of diagnostic techniques was assessed in 184 patients suspected of having pancreas cancer. Of 138 patients who were operated upon, 89 were found to have pancreas duct cancer, 30 had cancer of a different site of origin in the head of the pancreas region and in 19 there was no evidence of cancer at operation. All of the 46 patients who were not operated upon, 13 proven to have cancer and 33 patients discharged as free of cancer, were followed in our clinic. The majority of our patients presented with signs and symptoms of biliary obstruction. Computerized transaxial tomography (CTT) gave a “correct” diagnosis in 31 of 33 patients (94%) with proven cancer, there were 2 patients with a false negative report and a false positive diagnosis occurred in 8 of 20 patients (40%) without cancer. Celiac angiography (CA) gave a correct diagnosis in 78 of 94 patients (83%) with cancer, a false negative in 17%, and a false positive in 32%. 75Sele‐nomethionine pancreas scan correctly diagnosed 27 of 36 patients (75%) with cancer, gave a false negative in 25% and a false positive in 31%. Ultrasonog‐raphy gave a correct diagnosis in 18 of 27 patients with cancer (67%), a false negative in 33% and a false positive in 28%. Endoscopic retrograde cholangio‐pancreatography diagnosed correctly 8 of 11 cases (73%) of cancer, there were false negative diagnoses in 3 cases (27%) and false positives in 3 of 14 patients (21%). Duodenal aspiration techniques gave a very low percentage of correct diagnoses. Chronic pancreatitis most commonly gave rise to a false positive diagnosis. Serum alkaline phosphatase was elevated in 82% of patients, gave 18% false negatives and 33% false positives. Carcinoembryonic antigen (CEA) was elevated (> 2.5 ng/ml) in most of the pancreas cancer patients but also in patients with other cancers and with non‐cancerous diseases. In our hands, CTT, CA, alkaline phosphatase, 75Se‐methionine and ultrasonography, in descending order, have given the highest percentage of correct diagnoses but false positive and false negative diagnoses prevented any single test from being conclusive.

Acinar cell cystadenocarcinoma of human pancreas

A 7000 g cystic tumor replacing the body and tail of the pancreas was resected in a 64‐year‐old man. Numerous peritoneal implants confirmed its malignant nature. Light microscopy of both the primary tumor and the implants revealed distinctive cytoplasmic eosinophilia and apical granules. Ultrastructural examination demonstrated numerous zymogen granules and abundant, rough endoplasmic reticulum, which confirmed that the tumor was composed of acinar cells. No mucinous or serous differentiation was detected. We have not found report of a similar tumor.