Martin H. Kalser

Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group.

One‐hundred‐ninety‐four eligible and evaluable patients with histologically confirmed locally unresectable adenocarcinoma of the pancreas were randomly assigned to therapy with high‐dose (6000 rads) radiation therapy alone, to moderate‐dose (4000 rads) radiation + 5‐fluorouracil (5‐FU), and to high‐dose radiation plus 5‐FU. Median survival with radiation alone was only 51/2 months from date of diagnosis. Both 5‐FU‐containing treatment regimens produced a highly significant survival improvement when compared with radiation alone. Forty percent of patients treated with the combined regimens were still living at one year compared with 10% of patients treated with radiation only. Survival differences between 4000 rads plus 5‐FU and 6000 rads plus 5‐FU were not significant with an overall median survival of ten months. Significant prognostic variables, in addition to treatment, were pretreatment performance status and pretreatment CEA level.

Pancreatic cancer. Assessment of prognosis by clinical presentation

Three hundred ninety‐three patients who were entered into pancreatic carcinoma treatment protocols of the Gastrointestinal Tumor Study Group (GITSG) were analyzed as to significant differences in clinical presentation and factors influencing survival. Patients were grouped according to the stage of the disease. Group I (21 cases) included those patients who had a potentially curative resection. Group II(182 cases) patients had a locally unresectable tumor less then 400 cm2 (surgically proven) and no distant metastases, and Group III (190 cases) had advanced disease. Group I patients had the smallest lesions (median area, 9 cm2), located in head of the gland in 90% and painless jaundice was the most frequent clinical presentation (52%). In Group II, 83% were located in the head of the gland but the median area was much larger (36 cm2). Pain was present in 80% of cases, and jaundice in 62% with 48% having jaundice and pain. In Group III patients, lesions of body and tail were over four‐fold as frequent as in Group I and almost three‐fold greater than in Group II. The median area of the lesion was large (30 cm2). Pain was present in 85% and jaundice in only 31%. Median survival in Group I patients was longer than Group III (73 versus 10 weeks; P < 0.001). Ambulatory status, sex, race, abdominal pain, and histologic type influenced survival in one or more groups whereas age, jaundice, location of the tumor, degree of cellular differentiation, back pain, and nutritional status did not influence survival in any group. In all groups, those with a good performance status (Eastern Cooperative Oncology Group [ECOG] 0 and 1) survived longer than those with poor status (ECOG 2 and 3; P <0.05). The best potential prognosis is in those who are fully productive and present with painless jaundice, and who have resection of the tumor.

Randomized phase II clinical trial of adriamycin, methotrexate, and actinomycin-d in advanced measurable pancreatic carcinoma. A gastrointestinal tumor study group report

Sixty‐six patients with advanced pancreatic carcinoma were randomized to receive single agent chemotherapy with either adriamycin, methotrexate, or actinomycin‐D using conventional dose, route and schedule of administration. All patients had measurable lesions which were used for objective assessment of response. For adriamycin, 2 of 25 patients (8%) evidenced a partial response (2 of 15 (13%) previously untreated patients). One of 25 patients treated with methotrexate and one of 28 who received actinomycin‐D responded. The duration of responses ranged from 43–64 days for those patients with no chemotherapy prior to study entry. The median survival of patients who received adriamycin as initial treatment was 12 weeks compared to 8 weeks for methotrexate and 6 weeks for actinomycin‐D therapy.

Circulating carcinoembryonic antigen in pancreatic carcinoma.

Circulating CEA levels were determined in 102 patients with histologically proven pancreatic carcinoma and 26 patients with chronic pancreatitis. In the group with pancreatic carcinoma eleven patients had resectable tumors, the mean CEA in the nonjaundiced patients was 10 ± 5 ng/ml while the mean value in jaundiced patients in this group was 27 ± 40. Thirty‐four patients with nonmetastatic locally unresectable disease had a mean serum CEA of 25 ± 52 with a range of 1 to 250 ng/ml. Twenty‐one percent had values of 5 ng/ml or less. The mean value in 57 patients with metastatic disease was 97 ± 194 with a range of 0.5 to 1000 ng/ml and 19 percent had values of 5 ng/ml or less. Survival of patients with locally unresectable or metastatic carcinoma was significantly longer in those patients who had a normal CEA at the time of diagnosis. Circulating CEA in the metastatic group was much lower in patients with nonhepatic metastases as well as in those with well differentiated adenocarcinoma histology. Twenty‐three patients with chronic pancreatitis and normal serum bilirubin had a mean CEA value of 5.3 ± 4 ng/ml with 65% of values being 5 ng/ml or less but the CEA ranged from 4.6 to 27 in three who were jaundiced.

Azulfidine- (sulfasalazine-) induced hepatic injury

SummaryA patient with Azulfidine-related hepatotoxicity in which prompt recurrence of symptoms, fever, skin rash, and laboratory evidence of hepatocellular injury occurred upon readministration of Azulfidine is reported. The clinical and biochemical features support the fact that this was an example of an acquired hypersensitivity reaction to Azulfidine.

Blood Serotonin in Nontropical Sprue

Summary In 8 patients with nontropical sprue, blood or platelet serotonin levels, or both, were elevated during the active phase of the disease. In 2 of 3 patients the values reverted to normal during a remission induced by a gluten-free diet. There was no apparent correlation between the degree of steatorrhea and the serotonin abnormalities.

Cystadenocarcinoma and carcinoembryonic antigen (CEA).

A 40‐year‐old woman with back pain, an abdominal mass, and a serum CEA level of 200 ng/ml was found to have at laparotomy, a large but resectable mucinous retroperitoneal mass. Pathologic diagnosis revealed cystadenocarcinoma, probably of pancreatic origin. It is remarkable that the cyst fluid contained a CEA level 100,000‐fold normal. Serum CEA fell to normal levels in the postoperative period. This suggests that the CEA was of cyst epithelial origin.

Congenital Absence of the Gall Bladder with Choledocholithiasis: Literature review and discussion of mechanisms

Summary A case of agenesis of the gall bladder and cystic duct with associated choledocholithiasis and suppurative cholangitis has been presented. Incidence of the congenital disorder, its symptomatology and associated pathology have been reviewed. Mechanisms responsible for common duct dilatation in the absence of calculi as well as for the formation of calculi in the absence of the gall bladder are discussed. A rational therapeutic approach is outlined.

Relation of Osmolality to Jejunal Sorption of Water, Cations, and Glucose in Humans

Summary Net absorption and enterosorption of water, electrolytes, and glucose were determined in human subjects after the ingestion of solutions of isotonic electrolytes or of hypertonic glucose with electrolytes. After the ingestion of the isotonic solution there was, in the jejunum, a small but significant increase of osmolality (31 mOsm.) together with a significant absorption of water and an increase of sodium concentration as compared to the duodenum. As the hypertonic meal passed through the jejunal segment, absorption of water and glucose occurred simultaneously with a fall in osmolality from a mean of 548 mOsm. in the duodenum to a mean of 336 mOsm. in the jejunum. At the same time, the concentration of sodium and potassium increased. This suggests, within certain limits, that an hypertonic solution of glucose entering the jejunum is made isotonic primarily by the absorption of water and glucose rather than by exsorption of an hypotonic solution into the gut from the blood.

Defect in assimilation following combined radiation and chemotherapy in patients with locally unresectable pancreatic carcinoma.

The relative contributions of high‐dose irradiation and/or chemotherapy to the nutritional problems of patients with inoperable pancreatic carcinoma were evaluated by study of pancreatic exocrine function and jejunal function and morphologic findings in ten patients before and after treatment. Nutrient assimilation studies included determination of serum carotene levels, D‐xylose absorption and fat absorption. Crosby capsule biopsy specimen of jejunal mucosa were evaluated with light microscopy. Fat assimilation was the only parameter of nutritional function to significantly worsen after therapy. Low serum carotene levels present in the patients before therapy remained low but did not significantly change after treatment. D‐xylose absorption and the morphologic structure of the jejunal mucosa were normal before and after treatment. These findings support the previous observations that the nutritional problems of the patient with inoperable pancreatic carcinoma are due to pancreatic insufficiency and that high dose irradiation and chemotherapy can exacerbate the pancreatic insufficiency but do not produce jejunal dysfunction. Therefore, it is suggested that pancreatic exocrine replacement therapy may improve the nutritional status of these patients.