Combined modality treatment of localized unresectable adenocarcinoma of the pancreas.

Since 1978, 86 patients with unresectable localized adenocarcinoma of the pancreas have been treated with a combined modality program using radioactive iodine 125-Implantation, external beam radiation, and systemic chemotherapy. Three treatment approaches were used with sequential modifications of the technique based on the course of disease and patterns of failure. Group 1 was comprised of 13 patients treated with a combination of implantation followed by a planned external radiation dose of 5000 to 6000 cGy delivered in 6 weeks. Group 2 included patients treated as in Group 1 followed by adjuvant chemotherapy. The most recent group of 54 patients, Group 3, has been treated since 1981 with implantation into the tumor of radioactive Iodine 125 seeds (12000 cGy minimal peripheral dose), perioperative chemotherapy (5-FU, Mito-C), and external beam irradiation (5000-5500 cGy) followed by further chemotherapy. Incidence of perioperative mortality has been reduced from 31% (10/32) in Groups 1 & 2 to 7% (4/54) in Group 3. Clinical local control of tumor has been excellent in all three groups (84%). Analysis of the Group 3 results indicate that the problem of distant metastasis, in spite of adjuvant chemotherapy, still remains overwhelming (64%)--especially to the liver--and requires development of more effective regimens. Median survival in the three groups of patients is 5.5, 11.3, and 12.5 months. The 2-year survival is 0, 15, and 22%, retrospectively in the three groups.

Active specific immunotherapy of human solid tumors.

Active specific immunotherapy of human solid tumors by use of enzyme altered cells appears to be a feasible approach. Our initial results, we believe, warrant continued effort in this area. There seem to be no adverse clinical effects to such treatment. In vitro assay methods, to document enhanced immunity, must be included in any immunotherapy program. Equally importantly, such test methods should be expanded for the earliest detection of adverse effects, such as blocking during the course of immunotherapy. The role of immunotherapy must be that of adjuvant treatment, and its only applicability will be in that role.

Influence of antrectomy on gastrin release and gastric secretion in conscious monkeys.

The plasma-gastrin response to feeding and to insulin stimulation was determined before and after precise antrectomy in conscious rhesus monkeys (Macaca mulatta). Feeding resulted in a significant increase above basal gastrin levels (107 plus or minus 13 to 276 plus or minus 22 pg. per milliliter), as did stimulation with insulin (93 plus or minus 8 to 182 plus or minus 23 pg. per milliliter). Antrectomy reduced basal gastrin concentrations and abolished the gastrin response to both feeding and insulin. Antrectomy abolished the acid secretory response to histamine and insulin. In order to eliminate the problems of reflux gastritis and to study the time course of reduced acid secretory capacity, three monkeys were antrectomized and maintained by duodenal feedings. The histamine acid secretory response virtually was abolished within 24 hours and was not recovered over a 4 week period. Parietal cell architecture remained intact. In the monkey a major portion of basal circulating gastrin is antral in origin and the gastrin response to feeding and insulin is from the antrum exclusively. Loss of antral gastrin results in a virtual abolition of the acid secretory response to insulin and histamine. This decline is immediate in onset and is not related to parietal cell atrophy.

Rapid intra-abdominal spread of pancreatic cancer. Influence of multiple operative biopsy procedures.

Intra-abdominal spread of tumor is a common cause of treatment failure in patients with pancreatic cancer. We have reviewed 62 patients with pancreatic cancer undergoing repeat laparotomy in order to learn what factors are associated with the high risk of intra-abdominal metastases. Patients who underwent two or more operative biopsy procedures were at a markedly increased risk of developing intra-abdominal tumor seeding. These metastases were not detectable by preoperative computed tomography scan or ultrasound. This information affirms that multiple biopsies of pancreatic tumors increase the risk of local disease failure, and regimens based on nonoperative staging are likely to incorrectly minimize the extent of tumor involvement.

Five risk factors identify patients with gastroesophageal intussusception.

HYPOTHESIS: Risk factors in patients with gastroesophageal intussusception who have noncardiac chest pain need to be identified and analyzed. DESIGN: Prospective consecutive series of 43 patients with gastroesophageal intussusception. SETTING: Outpatient gastrointestinal endoscopy suite for 42 patients; 1 patient sustained gastroesophageal intussusception during labor and delivery and underwent an emergency laparotomy. INTERVENTION: Upper gastrointestinal tract endoscopy under intravenous sedation with appropriate monitoring of vital signs and photographic documentation in most patients. RESULTS: Gastroesophageal intussusception was documented endoscopically in 42 of 43 patients and was found to occur equally in men and women. Five risk factors have been identified: eating disorders or alcohol abuse, sudden sustained exertion, small-bowel obstruction, acid bile peptic disease, and pregnancy. Fifteen (70%) of 22 men were younger than 35 years; precipitating factors included sustained athletic effort and binge eating and drinking episodes. Fifteen (70%) of the 21 women were older than 35 years and had binge eating, peptic disease, and complications of pregnancy as risk factors. CONCLUSIONS: Five risk factors identify patients with severe vomiting or retching who are most likely to develop gastroesophageal intussusception, the precursor of a Mallory-Weiss tear. Upper gastrointestinal tract endoscopy with photographic documentation is the most accurate method of diagnosis. For most patients, medical management can reverse the cause of the vomiting. If vomiting is caused by mechanical obstruction or massive hemorrhage, surgical intervention may be necessary.

Alterations in lipogenic enzymes and lipoprotein lipase activity during gram-negative sepsis in the rat.

The effects of sepsis on lipid metabolism have not been clearly defined. This study was designed to observe the changes in adipose tissue lipoprotein lipase (LPL) and fatty acid synthetase (FAS) after administration of Escherichia coli bacteria. Male Lewis rats, weighing 245 to 270 g, were assigned to two groups and fed a powdered chow diet for 14 days. On day 14, one group was inoculated with E coli. Twenty-four hours later, both groups were killed by decapitation. Serum triglyceride levels were significantly elevated in the E coli-treated rats. Adipose tissue LPL and FAS activity was significantly decreased by 50% in E coli-treated rats compared with the control rats. These results suggest that the elevated serum triglyceride levels associated with sepsis maybe caused by a decreased rate of clearance of lipids from the blood and an increased rate of hepatic lipid synthesis.

Perfusion therapy for extremity melanoma.

Because of their initial appearance on extremities, malignant melanomas lend themselves to isolated chemotherapeutic perfusions. Perfusion is attractive because one can deliver effective cytotoxic drugs without systemic toxicity. We are reviewing 20 patients treated between 1960 and 1973 with isolated perfusion. Melphalan (L-phenylalanine mustard) was the drug of choice. Eleven of the 20 patients had previous surgical treatment. Three of the 11 patients are still alive from 27 to 72 months postperfusion. Eight died after an average survival time of 33 months. Of the seven patients who underwent perfusion as primary therapy, four patients are alive from 25 to 76 months postperfusion, and three died after an average survival time of 34 months. There is direct correlation between stages and levels of melanoma, and perfusion and prolonged survival time.

Cell-mediated immunity in patients with renal cell carcinoma as measured by leukocyte migration inhibition test.

The cell-mediated immune (CMI) response to tumor-associated antigens present in 3 M KCL extracts of renal cell carcinoma tissue was measured in patients with renal cell carcinoma (RCC) by the leukocyte migration inhibition (LMI) test. Of 30 patients with histologically proved RCC, 19 (63%) gave a positive LMI test; whereas, 2 of 28 (7%) of the normal donors, 13 of 43 (30%) patients with other cancers, and 5 of 14 (36%) benign kidney disease patients gave positive tests. Thirteen per cent of RCC patients reacted to a normal kidney extract. Although 33% gave a positive response to a lung carcinoma extract, the incidence of reactivity was less than that observed with the lung cancer patients. These results suggest that a CMI response to a renal carcinoma-associated antigen was measured by the LMI test. Correlation of the LMI data with the stage of disease and clinical status indicated that 71% of patients that had a localized tumor and were clinically free of disease one year postnephrectomy lost their tumor-directed CMI response. Patients with distant metastasis (Stage D) were LMI positive provided they had not received radiation or hormone therapy at the time of testing. These results suggest that the demonstration of CMI, as measured by the leukocyte migration inhibition test, correlates with the presence of active disease.

The consequences of a major bile duct injury during laparoscopic cholecystectomy.

Bile duct injury is perhaps the most feared complication of laparoscopic cholecystectomy. The focus of this study was on the immediate and short-term outcome of patients who have undergone repair of major bile duct injuries with respect to hospital stay, perioperative interventions, and reoperations. The records of patients who underwent surgery at three academic hospitals in Philadelphia (Hospital of the University of Pennsylvania, Thomas Jefferson University Hospital, and Graduate Hospital) from 1990 to 1995 for repair of a major biliary injury following laparoscopic cholecystectomy were reviewed. A major biliary injury was defined as any disruption (including ligation, avulsion, or resection) of the extrahepatic biliary system. Small biliary leaks not requiring surgery were excluded. Thirty-two patients sustained major bile duct injuries. The injury was recognized immediately in 10 patients. The remaining 22 patients had pain (59%), jaundice (50%), and/or fever (32%) as the symptom heralding the injury. Bismuth classification was as follows: 13% of patients were class I, 63% were class II, 7% were class III, 7% were class IV, and 10% were class V. Biliary reconstruction included a Roux-en-Y hepaticojejunostomy in 30 patients and two were primary repairs. There was one postoperative death from multiorgan system failure. The mean length of hospital stay after repair was 17 +/- 8 days. Over a mean follow-up period of 11.5 +/- 10.5 months, 11 patients (38%) required 19 emergency readmissions, most commonly for cholangitis. Five patients (17%) required postoperative balloon dilatation for biliary stricture. At follow-up 18 patients (62.0%) remain asymptomatic with normal liver function, eight (28%) are experiencing episodic cholangitis, and three (10%) are asymptomatic with persistently elevated liver function values. The consequences of a major biliary tract injury following laparoscopic cholecystectomy include a complex operative repair resulting in a lengthy postoperative stay with an increased risk of death, an excessive number of perioperative diagnostic and therapeutic studies, frequent readmissions (often as emergencies), and a lifelong risk of restricture. The "cost" to these patients remains enormous.

Bilateral adrenalectomy in treatment of disseminated breast cancer.

Forty-three patients underwent bilateral adrenalectomy for advanced breast cancer at the Hospital of the University of Pennsylvania from 1960 to 1974. Fourteen patients (32 per cent) experienced an objective remission. There was no difference in the initial free interval between the responders and nonresponders. Premenopausal patients who improved after surgical castration or androgen therapy and postmenopausal patients who responded to estrogen therapy and its subsequent withdrawal had a greater response to adrenalectomy. Twenty-three of the forty-three patients who underwent bilateral adrenalectomy had evidence of metastatic involvement in at least one of the excised adrenal glands. Results show that patients who responded to previous therapy had a longer survival after adrenalectomy.

Changes in circadian rhythmicity of liver and serum parameters in rats fed a total parenteral nutrition solution by continuous and discontinuous intravenous or intragastric infusion.

Circadian rhythms were assessed in rats (224-246 grams) receiving either an intragastric (IG) or intravenous (IV) infusion continuously (C), or IG or IV infusions discontinuously (D) from 0000 to 1400 hours daily. A control group was maintained on a stock diet ad libitum. IV- and IG-fed rats were infused with 50 milliliters per day of a solution containing 25% dextrose and 4.25% amino acids plus vitamins and minerals. After 10 to 11 days, groups of rats were killed from each treatment every 6 hours over a 24-hour period. Results showed that IG feeding promoted better growth and nitrogen retention than IV feeding. Rhythm patterns for liver weight, glycogen, and protein content were similar between D-IG and D-IV infused rats. All groups except the D-IV fed rats exhibited fluctuations of serum insulin. A rhythm was not present for serum glucose in C-IV fed rats and a rhythm was also absent for serum albumin in both C-IV and D-IV fed rats. C-IV feeding increased serum glucose and insulin levels and decreased serum albumin levels in comparison to IG feeding. In comparison to the ad libitum-fed, control rats, C-IV or D-IV or IG infusions led to alterations in liver and serum parameters.

The use of autografts for vertebral body replacement of the thoracic and lumbar spine.

Thirty-seven patients with fractures of the thoracic or lumbar spine underwent anterior corpectomy (partial or complete) and vertebral body replacement for either destructive lesions from tumor or infection (13 patients) or trauma (24 patients). The vertebral bodies were replaced using either rib (12 patients) or tricortical iliac crest (25 patients) autografts. The Dunn device was utilized in conjunction with the autografts in 19 patients. Posterior stabilization was used in five patients; three prior to anterior stabilization and two after anterior stabilization. Within 2 weeks of the operative procedure, all patients began walking or sitting. Of the 37 patients, 21 with incomplete neurologic deficits improved, and 10 of those went onto complete recovery. Of the 27 patients who have been followed for a minimum of 1 year, 25 have obtained solid fusions, one developed a pseudarthrosis that required regrafting, and one had a delayed union prior to death from metastatic disease. There were two deaths in the immediate postoperative period and three deaths in the first six postoperative wounds due to metastatic disease. The purpose of this study is to present a consecutive series of patients who have undergone corpectomy and vertebral body replacement as well as to define the adequacy of stabilization.

Chemoneurolysis of the canine gastric submucosa: modification of surgically-induced peptic ulcer formation.

Chemoneurolysis of the canine antral submucosa with 25% ethyl alcohol solutions reduced ulcer formation and increased the survival times in animals subjected to the Exalto-Mann-Williamson ulcer-producing procedure.

Malignant melanoma--an overview.

We have presented our experience in light of current practice in the management of malignant melanoma. Central to considerations of adequate management is the question of precise definition of the extent of the disease as determined by histologic evaluation, determination of the depth of penetration and assessment of the extent of spread. Wide surgical excision remains the most important consideration with perfusion therapy, in our view playing a key role in the management of extremity melanoma. Encouraging data for adjuvant immunotherapy continues to unfold. We present here a rational approach to diagnosis and management of malignant melanoma.

Management of infected pancreatic fluid collections.

Percutaneous drainage of pancreatic collections has recently been advocated as a means of diagnosis of bacterial contamination, for temporizing unstable patients, and as definitive treatment in itself. In order to assess its efficacy, the role of percutaneous drainage of infected pancreatic fluid collections was retrospectively reviewed by a single surgical practice. Seventeen patients were treated over a 5-year period from 1987 to 1992. All patients admitted or referred with a diagnosis of infected peripancreatic fluid collection were included in the review. The group consisted of eleven males and six females; mean age was 55.2 years (range 28 to 70). Patients were stratified into one of two groups based on initial treatment modality. Group A consisted of eight patients treated initially with percutaneous drainage as presumed definitive management. Eight patients in Group B were treated initially with surgical debridement and drainage. APACHE II scores on admission were 5.62 +/- 3.66 for Group A and 9.12 +/- 3.87 for Group B (N.S.). Mean hospital stay was 100 days (range 13-311) for Group A and 71 (range 25-149) for Group B (N.S.). Despite initial percutaneous drainage, six of eight (75%) patients in Group A required operative debridement because of clinical deterioration. APACHE II scores in this subset went from 6.83 +/- 3.43 to 9.83 +/- 5.04 (N.S.) despite a total of 18 preoperative percutaneous procedures (2.25 per patient; range 1-7). The number of complications for this group totaled 15. Five of the six patients with positive cultures from their initial aspiration failed percutaneous drainage.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemoneurolysis of the canine gastric submucosa. Effects on surgically-induced gastric hypersecretion on the Heidenhain pouch.

Double denervated gastric pouches were constructed in dogs. One gastric pouch served as a control, and the other gastric pouch had its submucosa infiltrated with 25% ethyl alcohol, (submucosal chemoneurolysis). Neurolysis of these gastric pouches eliminated their gastric secretory responses to histamine, meat and pentagastrin without altering their histological appearance. Transplantation of 75% of the gastric antrum into the colon caused a hypergastrinemia and increased the sensitivity of the control gastric pouches to the various stimuli but had no such effect on those gastric pouches infiltrated with ethyl alcohol.

Chemoneurolysis of the canine gastric submucosa. Effects on Heidenhain pouch secretion.

Double denervated gastric pouches were constructed in dogs. One gastric pouch served as a control, and the other gastric pouch had its submucosa infiltrated with 25% ethyl alcohol (submucosal chemoneurolysis). Neurolysis of these gastric pouches did not alter their histological appearance but did eliminate their gastric secretory responses to histamine, meat and pentagastrin. The dogs exhibited elevated serum gastrin levels after feeding.

Changes in the activities of lipoprotein lipase and the lipogenic enzymes in tumor-bearing rats.

The effects of tumor growth on lipid metabolism were investigated by evaluating serum lipids, lipoprotein lipase activity (LPLA), the lipogenic enzymes, urinary catecholamines along with serum insulin and glucagon levels. We injected 1.5 X 10(6) cells of rat mammary tumor, AC33, and killed the rats on the 18th day. Serum triglycerides and free fatty acids of the tumor-bearing (TB) rats increased 4 and 5 times, respectively, more than the control (C) rats. Total liver lipids were not significantly different between the two groups. Tumor growth produced a 70% decrease in total epididymal fat pad LPLA; there were no changes in soleus muscle LPLA. Serum insulin levels of the TB rats were 49% less than the C rats. The TB rats had significantly lighter epididymal fat pads and lower activities of adipose fatty acid synthetase and citrate cleavage enzyme. Urinary catecholamines of the TB rats were reduced over 30% compared with the C rats. These results show that the hypertriglyceridemia of the TB rats may be due, in part, to a deficiency of adipose tissue LPLA. The data also suggest that the effects of the tumor on lipid metabolism may be mediated through insulin.

Silicone prostheses and anti-tumor immunity: an in-vitro rat study.

We believe we have demonstrated that there is no difference in the immune responsiveness in normal animals which undergo sham surgery (as compared to those unoperated). With the addition of a simple placement of a silicone prosthesis, there was an increase in the lymphocyte cytotoxicity--but this was equalized by a blocking effect at both the target cell and the lymphocyte levels. This response appeared to be of short duration. The presence of tumor, as previously documented produces an increase in lymphocyte cytotoxicity with a concomitant increase in the target cell and the lymphocyte blocking effect. Importantly, we found no significant difference in the immune response when prostheses were placed as an adjunct to surgical excision of transplanted tumors in this rat model.

Cancer of the colon and rectum. A review.

Colonic cancer remains a major cause of death because diagnosis is usually delayed. Improved methods for earlier detection will maximize the patient's chances for survival. At present, surgery offers the greatest possibility of cure, but even in those instances where less than definitive resection is possible, there is much in the way of adjunctive and palliative therapy to offer the patient.