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Biomedical subjects

L E Harrison

Publications and source records attributed to L E Harrison.

At least 37 records · Page 2Linked to original sources

Phenylacetate inhibits isoprenoid biosynthesis and suppresses growth of human pancreatic carcinoma.

BACKGROUND: Phenylacetate is growth inhibitor for a variety of tumors at concentration that have been safely achieved in human beings. This antitumor effect is related to inhibition of the isoprenoid synthetic pathway by blocking the enzyme, mevalonate pyrophosphate (MVAPP) decarboxylase. The purpose of this study was to evaluate the effects of phenylacetate on human pancreatic carcinoma. METHODS: For in vitro studies, six human pancreatic carcinoma cell lines (BxPc, AsPc, MIAPaCa-2 Panc-1, CFPAc, and HS 766T) were studied. For in vivo studies, nude mice were inoculated with pancreatic cells (BxPc and MIA PaCa-2) and randomized to receive phenylacetate or saline control. RESULTS: Phenylacetate produces reversible in vitro growth arrest at doses of 2.5 to 10 mmol. The antiproliferative effect is cytostatic, producing accumulation of cells in G1, and is not associated with cell toxicity. Systemic treatment of nude mice bearing heterotopic human pancreatic carcinoma results in growth inhibition of tumors without host toxicity. Phenylacetate blocks the processing of mevalonate to isopentenyl-pyrophosphate by inhibiting MVAPP and exhibits suppression of biosynthetic pathways requiring isoprenoids, including cholesterol and dolichol biosynthesis, protein glycosylation, and isoprenylation of proteins. CONCLUSIONS: These results indicate that phenylacetate has cytostatic activity in pancreatic carcinoma and support the conclusion that suppression of multiple biosynthetic pathways requiring isoprenoids is contributing to the drug's antiproliferative action. The safety profile and efficacy of phenylacetate make it an attractive agent for the treatment of pancreatic cancer.

Animals↗

The role of dietary factors in the intestinal and diffuse histologic subtypes of gastric adenocarcinoma: a case-control study in the U.S.

BACKGROUND: The decline of gastric adenocarcinoma in the U. S. and the parallel decrease in the predominance of the intestinal type of gastric adenocarcinoma may reflect, in part, changes in diet over the last 60 years. Because the intestinal and diffuse types of gastric adenocarcinoma may be epidemiologically distinct, the authors hypothesized that different nutritional factors are associated with the different subtypes of gastric adenocarcinoma. METHODS: Ninety-one incident cases with a pathologic diagnosis of gastric adenocarcinoma and 132 cancer free controls were included in this study. All cases were defined as being either the intestinal or diffuse type of gastric adenocarcinoma. Epidemiologic data were collected by a modified National Cancer Institute Health Habits History Questionnaire. Nutritional and dietary factors were analyzed using a logistic regression model. RESULTS: Several dietary factors were significantly associated with both subtypes of gastric adenocarcinoma, including dietary intakes of fiber, oleic acid, potassium, and fruits. Almost all dietary factors and food groups unique to intestinal gastric adenocarcinoma were protective in nature (vitamin B6, folate, niacin, iron, noncitrus fruits, and raw fruit), except for a high intake of dietary calories, which was a risk factor for intestinal gastric adenocarcinoma. The unique factors found to be protective for diffuse disease were carbohydrate and vitamin C intake. CONCLUSIONS: This study suggests that dietary factors contribute to the carcinogenesis of gastric adenocarcinoma. It also appears that although dietary risk and protective factors are common to both the intestinal and diffuse types of this malignancy, protective dietary factors may play a more important role in preventing the intestinal type of gastric adenocarcinoma.

Adenocarcinoma↗

Gastric remnant carcinoma: just another proximal gastric cancer or a unique entity?

BACKGROUND: Gastric cancer that occurs 5 or more years after distal gastric resection for benign disease is defined as gastric remnant carcinoma (GRC). The purpose of this study was to determine whether postresection outcome differs between GRC and primary proximal gastric cancer (PPGC). METHODS: Twenty-five patients with GRC who underwent resection between August 1985 and July 1994 were compared with 79 PPGC patients who underwent resection during the same time period. RESULTS: Overall actuarial 5-year disease-specific survival was 63% for curatively resected GRC patients and 37% for the curatively resected PPGC patients (P = 0.1, log rank). No significant differences in survival were seen between the two groups when stratified for stage. On multivariate analysis of significant predictors of outcome for the 104 patients as a group, only the ability to do a curative resection was significant. CONCLUSION: The outcome following resection of GRC is no different from that of other primary proximal gastric cancers of the same stage. Every effort should be made to perform a curative resection, as this is a significant predictor of outcome.

Aged↗

Early postoperative enteral feeding improves whole body protein kinetics in upper gastrointestinal cancer patients.

BACKGROUND: Patients with upper gastrointestinal (GI) tract malignancies are at increased risk for malnutrition, as well as postoperative morbidity and mortality. As data clearly documenting the benefit of early postoperative enteral feeding in upper GI cancer patients as compared with no feeding are sparse, we examined the protein kinetic effects of early enteral feeding and compared it with standard postoperative care (ie, intravenous fluid). METHODS: Twenty-nine patients undergoing resection of an upper GI tract malignancy were prospectively randomized to either enteral feeding (FEED, n = 12) starting on postoperative day (POD) 1 via a jejunostomy tube or intravenous fluid (IVF, n = 17). On POD 5, all patients underwent resting energy expenditure determination and a protein metabolic study using the isotope 14C-leucine to determine whole body (WB, micromol leu/kg/min) protein kinetics. RESULTS: Respiratory quotient and insulin (microU/mL) levels were significantly increased in patients receiving enteral feeding (0.85 +/- 0.02, 19.8 +/- 4.5 versus 0.78 +/- 0.02, 9.3 +/- 0.8, FEED versus IVF, P < 0.05). Free fatty acids (meq/dL) were significantly lower in FEED group (0.36 +/- 0.04) as compared with IVF group (0.85 +/- 0.07, P < 0.0001). While there were no significant differences in WB protein oxidation (0.10 +/- 0.01 versus 0.10 +/- 0.02) or synthesis (0.81 +/- 0.09 versus 0.68 +/- 0.08, IVF versus FEED), WB protein catabolism was significantly less (0.91 +/- 0.10 versus 0.37 +/- 0.09, P = 0.002), and WB protein net balance was converted to positive in FEED group (-0.10 +/- 0.01 versus 0.30 +/- 0.03, IVF versus FEED, P < 0.001). CONCLUSIONS: Early enteral feeding decreases fat oxidation and whole body protein catabolism while improving net nitrogen balance. By significantly improving protein metabolism, enteral feeding may decrease postoperative morbidity and mortality in upper GI cancer patients.

Aged↗

Pancreaticoduodenectomy for nonperiampullary primary tumors.

INTRODUCTION: This review was performed to evaluate the outcome of patients undergoing pancreaticoduodenectomy (PD) for isolated metastatic or locally advanced nonperiampullary tumors at a single institution over a 13-year period. METHODS: Between 1983 and 1996, patients undergoing PD for metastatic or locally advanced nonperiampullary malignancies were identified. Medical records were reviewed and outcome factors and survival data analyzed. RESULTS: Eighteen patients were identified. The primary tumor histopathology included colon (n = 7), gastric (n = 4), renal cell (n = 3), lung (n = 2), bladder (n = 1), and melanoma (n = 1). The median length of hospital stay was 15 days (6 to 48) with one perioperative death (5.5%). The median tumor size was 5.5 cm (0.8 to 11.5), and 7 patients had positive peripancreatic lymph nodes. The median survival was 40 months, with a 5-year survival of 35%. CONCLUSIONS: Pancreaticoduodenectomy for nonperiampullary malignancy is infrequently indicated. However, in the absence of widely metastatic disease, PD should be considered for locally advanced tumors or isolated metastatic malignancy.

Carcinoma, Renal Cell↗

Hepatic resection for noncolorectal, nonneuroendocrine metastases: a fifteen-year experience with ninety-six patients.

BACKGROUND: The role of liver resection for hepatic metastases from noncolorectal, nonneuroendocrine (NCNN) cancers is unknown. This study examines a large, single institutional experience of hepatic resection for NCNN metastases. METHODS: Records of 96 patients who underwent liver resection for metastatic NCNN cancer from 1980 to 1995 at a single institution were reviewed. Survival after liver resection in this cohort of patients is reported, and factors predictive of survival are analyzed. RESULTS: Resection was performed for liver metastases from genitourinary primary tumors (n = 34), soft tissue primary tumors (n = 41), and metastases from other primary cancers (n = 21). Extent of liver resection included wedge (n = 32), lobectomy (n = 44), and extended hepatic lobectomy (n = 20). No operative deaths occurred. Overall survival rate after resection at 1, 3, and 5 years was 80%, 45% and 37%, respectively (median survival, 32 months), with 12 actual 5-year survivors. There was no difference in survival according to the type of liver resection, bilateral versus unilateral disease, or resection of extrahepatic disease. Disease-free interval of less than 36 months before discovery of liver metastases, curative resection, and primary tumor group (genitourinary was greater than soft tissue, which was greater than gastrointestinal) were predictors of a significantly better survival by multivariate analysis. CONCLUSIONS: Primary tumor type, disease-free interval, and curative resection predict those patients who benefit from hepatic resection. Hepatic resection for patients with NCNN metastasis has value in carefully selected patients.

Adult↗

Preoperative carcinoembryonic antigen predicts outcomes in node-negative colon cancer patients: a multivariate analysis of 572 patients.

BACKGROUND: Although prospective trials have demonstrated that postoperative chemotherapy for node-positive colon cancer patients provides survival benefit, no improvement in survival has been documented for node-negative colon cancer patients. There are, however, a subset of node-negative patients that go on to die of their disease. We hypothesize that this subset of node-negative patients may benefit from postoperative chemotherapy. We analyzed a large cohort of node-negative colon cancer patients from a single institution to determine prognostic factors that predict which patients with node-negative colon cancer might experience recurrence and can benefit from postoperative chemotherapy. STUDY DESIGN: A review of the prospective database for colorectal cancer at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1985 and 1993 identified 572 patients who underwent curative resection for node-negative colon cancer (T(1,2,3,4)N0M0). Demographic, serum, and pathologic factors were analyzed for prognostic significance. Survival was calculated by the method of Kaplan-Meier and compared by log rank test. Multivariate analysis was calculated by the Cox proportional hazard model. RESULTS: Median follow-up was 35 months. Factors predictive of survival by univariate analysis include tumor stage, overall stage, and preoperative serum carcinoembryonic antigen (CEA) elevation. By multivariate analysis, overall stage and preoperative serum CEA level predicted survival. CONCLUSIONS: Routine histologic and demographic factors do not predict outcome in node-negative colon cancer patients. Preoperative CEA and overall stage predict survival by multivariate analysis. Preoperative CEA elevation in node-negative patients identifies a group of patients that has a poor prognosis and defines a subset of patients who may benefit from postoperative chemotherapy.

Adult↗

Proximal gastric cancers resected via a transabdominal-only approach. Results and comparisons to distal adenocarcinoma of the stomach.

OBJECTIVE: The purpose of this study is to compare the outcome of patients with proximal gastric cancer (PGC) treated by a transabdominal-only resection to that of patients with distal gastric cancer (DGC). SUMMARY BACKGROUND DATA: It has been suggested that PGC is inherently more aggressive than DGC. The worse survival of PGC compared with that of DGC may be in part, because of the difficulty distinguishing PGC from distal esophageal adenocarcinoma. By defining a subset of PGC resected using an transabdominal-only approach, one may discriminate true PGC from distal esophageal adenocarcinoma. This subset of patients is a more appropriate comparison group when analyzing outcome relative to patients with DGC. METHODS: A review of the prospective database for gastric adenocarcinoma at Memorial Sloan-Kettering Cancer Center between July 1985 and August 1995 identified 98 patients with PGC resection via a transabdominal-only approach. Of these, 65 underwent proximal gastrectomy and 33 underwent total gastrectomy. For DGC, 258 required a distal gastrectomy and 71 required total gastrectomy. RESULTS: The overall 5-year survival of patients with PGC was 42% (median survival, 47 months), whereas the 5-year survival for patients with DGC was 61% (median survival, 106 months, p = 0.03). Within each stage, there were no significant survival differences, but in all stages, survival was better for patients with DGC. More important, the site of the primary tumor appears to affect survival, with a worse outcome as the tumor moves proximally. CONCLUSIONS: Despite excluding distal esophageal cancers, survival for patients with PGC remains worse than for those with DGC. Late stage of presentation could not explain this difference. It appears that PGCs are inherently more aggressive than are DGCs. In addition, site of the primary tumor appears to affect outcome, with a trend toward a worse outcome as the tumor moves proximally.

Adenocarcinoma↗

Portal vein involvement in pancreatic cancer: a sign of unresectability?

Although the prognosis remains poor, surgical exploration with complete resection provides the only potential cure for patients with adenocarcinoma of the pancreas. However, only 15% to 20% of patients are candidates for resection because of the presence of distant tumor outside the confines of resection or because of locally advanced disease. Even though isolated portal vein involvement has classically been a contraindication for resection, PVR can be performed safely with a low perioperative mortality rate. Besides PV involvement and size, the distribution of histopathologic prognostic factors is no different between patients undergoing PVR and those undergoing standard pancreatic resection. Importantly, overall survival is similar between both groups. Therefore, suspected isolated PV involvement frequently does not preclude operability and, by itself, should not be a contraindication to pancreatic resection.

Adenocarcinoma↗

gamma-Glutamyl transpeptidase mediation of tumor glutathione utilization in vivo.

BACKGROUND: Glutathione is a tripeptide used by cells to protect against oxidative and free radical damage. It may also be involved in biochemical mechanisms that cause some tumors to become resistant to anticancer drugs. gamma-Glutamyl transpeptidase (GGTP) is a membrane-bound enzyme that cleaves extracellular glutathione, providing cells with amino acids necessary for intracellular synthesis of this compound. Increased expression of GGTP has been found in a number of human tumors; however, few studies have examined the contribution of GGTP to tumor glutathione metabolism in vivo. PURPOSE: Our goals were to study the utilization of host glutathione by 3-methylcholanthrene (MCA)-induced sarcomas grown in rats and to evaluate the involvement of tumor GGTP in this process. METHODS: The left ovaries of 21 female Fischer 344 rats were isolated by laparotomy and placed in subcutaneous positions through stab wounds in the abdominal wall. A 3-mm cube of MCA sarcoma was then sutured to each of the isolated ovaries. The MCA implants obliterated the ovarian tissue, yielding isolated tumors with one arterial supply (the ovarian artery) and one draining vein (the ovarian vein, referred to as the tumor vein). After 2 weeks of tumor growth, blood was drawn from the tumor vein, the inferior vena cava (IVC), and the aorta of 16 animals. Glutathione and cysteine concentrations in plasma samples from this blood were determined by high-performance liquid chromatography and used to calculate glutathione and cysteine utilization ratios for the tumor and the systemic circulations ([(concentration aorta-concentration tumor vein)/concentration aorta] x 100 and [(concentration aorta-concentration IVC)/concentration aorta ] x 100, respectively). The utilization ratios from these control animals were compared with those from acivicin (AT-125; an irreversible GGTP inhibitor)-treated rats (the remaining five animals). Data are presented as mean +/- standard deviation; reported P values are from two-tailed tests of statistical significance. RESULTS: In the control animals, glutathione and cysteine concentrations were significantly lower in the tumor vein (3.55 +/- 1.9 and 5.69 +/- 2.8 microM, respectively) and in the IVC (5.65 +/- 2.3 and 7.17 +/- 2.4 microM, respectively) than in the artery (12.48 +/- 5.7 and 12.33 +/- 5.9 microM, respectively; all P values < .05). In addition, the glutathione utilization ratio was significantly higher for the tumor circulation than for the systemic circulation (69% +/- 14% versus 52% +/- 14%; P < .003). The combined glutathione and cysteine utilization ratio was also significantly higher for the tumor circulation than for the systemic circulation (116% +/- 35% versus 88% +/- 28%; P < .02). Treatment with AT-125 lowered the tumor glutathione utilization ratio significantly (45% +/- 12% for treated animals versus 69% +/- 14% for control animals; P < .005). CONCLUSIONS: Our results show that glutathione and cysteine in the host circulation are used by MCA sarcomas. The significant reduction in tumor utilization of serum glutathione after treatment with AT-125, a GGTP inhibitor, indicates that GGTP is important in tumor glutathione metabolism.

Animals↗

Effect of human growth hormone on human pancreatic carcinoma growth, protein, and cell cycle kinetics.

The role of human growth hormone (hGH) as a nutritional adjunct for cancer patients is controversial because of its potential mitogenic effects on tumor growth. No studies to date have examined the effect of hGH on human tumor response in vivo. In Vitro: Athymic mice were injected (s.c.) daily with hGH (GH, n=14) or saline (CTL, n=14). On Day 10, serum was collected and added to human pancreatic carcinoma cells in culture. In Vivo: Athymic mice were inoculated (s.c.) with human pancreatic carcinoma cells. On Day 14, mice were randomized to receive daily either hGH (GH, n=14) or saline (CTL, n=12). On Day 29, animals received [3H]phenylalanine for tissue protein fractional synthetic rate (FSR) measurement. Tumors were excised and cell cycle kinetics analyzed. Data are expressed as mean +/- SEM. Statistical analysis was performed by unpaired t test and/or ANOVA where appropriate. In Vitro: Serum from GH-treated animals had elevated IGF-1 levels (287 +/- 34 ng/ml vs 157 +/- 53 ng/ml, P<0.001) and significantly stimulated cell growth (No. cells x 10(3)/well) compared with CTL serum (925 +/- 31 vs 747 +/- 38, P<0.001). In Vivo: Serum for GH-treated animals had elevated IGF-1 levels (287 +/- 34 ng/ml vs 157 +/- 53 ng/ml, P<0.001) and significantly stimulated cell growth (No. cells x 10(3)/well) compared with CTL serum (925 +/- 31 vs 747 +/- 38, P<0.001). In Vivo: Growth hormone had no significant effect on tumor growth rate (mm3/day) (1.45 +/- 0.47 CTL vs 1.57 +/- 0.66 GH), final tumor weight (mg) (0.19 +/- 0.15 CTL vs 0.17+/- 0.06 GH), DNA Index (1.5 +/- 0.1 CTL vs 1.5 +/- 0.1 GH), percent S phase (20.3 +/- 3.3 CTL vs 22.1 +/- 3.0 GH), or tumor FSR (%/day) (51.1 +/- 17.8 CTL vs 70.2 +/- 61.1 GH). Growth hormone significantly elevated serum IGF-1 levels (ng/ml) (176 +/- 48 CTL vs 222 +/- 53 GH, P<0.005) and liver FSR (%/day) (62.8 +/- 17.8 CTL vs 79.7 +/- 12.7 GH, P<0.005). Serum of GH-treated mice increased human pancreatic cell growth in vitro. In vivo, GH administration raised serum IGF-1 levels and increased liver protein FSR, without tumor growth, cell cycle kinetics, or protein FSR.

Animals↗

Selective glutathione repletion with oral oxothiazolidine carboxylate (OTZ) in the radiated tumor-bearing rat.

Oxothiazolidine carboxylate (OTZ) is a cysteine prodrug which augments intracellular glutathione (GSH) levels. We examined the effects of oral OTZ on tumor and host tissue reduced GSH levels in fasting and radiated models of GSH depletion. In addition, we studied the tumor's ability to utilize OTZ via the enzyme, oxoprolinase. Fischer 344 rats (n = 40) were implanted with MCA sarcoma and studied at 10% tumor burden. Treatment consisted of 10 mmol/kg OTZ or buffer orally. After a 24-hr fast, 16 animals were treated and tumor, kidney, jejunal, and colonic mucosa were collected after 4 hr. Significant increases in GSH with OTZ (n = 8) vs buffer (n = 8) were seen in kidney (5.6 +/- 0.4 vs 4.3 +/- 0.9; P < 0.01), jejunum (13.8 +/- 1.3 vs 12.1 +/- 1.1; P < 0.05), and colon (6.7 +/- 1.2 vs 5.3 +/- 0.6; P < 0.05), but not tumor (8.9 +/- 2.4 vs 10.6 +/- 1.4; P = 0.12). Sixteen animals were treated 4 hr before and 18 hr following 1100 cGy of abdominal radiation and at 4 days, tumor, jejunal, and colonic mucosa were collected. Significant increases in GSH with OTZ (n = 8) vs buffer (n = 8) were noted in jejunum (9.3 +/- 1.1 vs 7.5 +/- 1.8; P < 0.05) and colon (5.6 +/- 1.1 vs 4.3 +/- 0.9; P < 0.05) but not tumor (8.4 +/- 1.6 vs 7.6 +/- 1.4; P = 0.34). To determine tissue oxoprolinase activity, tumor, kidney, liver, jejunal, and colonic mucosa were collected from 8 animals. Oxoprolinase activity was highest in the kidney (814 +/- 145) with no difference noted between liver and tumor (280 +/- 117 and 324 +/- 137, respectively). Oral OTZ selectively increases reduced GSH levels in normal tissues compared to tumor following fasting and whole abdominal radiation. This increase does not appear to be due to a differential activity of oxoprolinase. OTZ may have a role in protection against toxicity associated with oxidative injury by selective repletion of normal host tissue GSH levels.

Administration, Oral↗

Depletion of high energy phosphate compouds in the tumor-bearing state and reversal after tumor resection.

BACKGROUND: Cancer cachexia is a syndrome manifested by a variety of metabolic abnormalities that include depletion of host energy stores. We studied liver and skeletal muscle high energy phosphate compounds, inorganic phosphorus (Pi), and the energy charge in tumor-bearing (TB), pair fed non-tumor-bearing (NTB), and tumor-bearing resected (RES) rats. METHODS: F344 rats were randomized into TB (n = 13), NTB (n = 13), and RES (n = 5) groups. On day 0, the flanks of the TB and RES animals were injected with 1 x 10(7)n methylcholanthrene (MCA)-induced sarcoma cells. On day 19, TB and NTB rat liver and skeletal muscle were analyzed for adenine nucleotides, phosphocreatine, and Pi, and RES animals underwent tumor resection followed by tissue analysis 10 days later. RESULTS: Although the liver adenylate energy charge was maintained, the level of liver adenosine monophosphate was significantly increased and the liver adenosine diphosphate level was decreased in the TB animals (3.55 +/- 0.6, 3.70 +/- 0.3 mumoles/gm dry weight, p < 0.05, p = 0.05, respectively) when compared with the NTB animals (3.06 +/- 0.4, 4.00 +/- 0.5 mumoles/gm dry weight, respectively). Muscle adenosine diphosphate levels were significantly decreased in the TB animals (1.57 +/- 0.7 mumoles/gm dry weight) as compared with NTB animals (2.23 +/- 0.7 mumoles/gm dry weight, p < 0.05). In addition, muscle adenosine triphosphate, phosphocreatine, and phosphocreatine/adenosine triphosphate ratios were significantly decreased in TB animals (19.94 +/- 4.5, 81.51 +/- 12.8, and 4.20 +/- 0.8 mumoles/gm dry weight, respectively) as compared with NTB animals (24.44 +/- 1.9, 116.72 +/- 7.5, and 4.81 +/- 0.4 mumoles/gm dry weight, respectively, p < 0.05) and RES animals (24.08 +/- 3.3, 124.10 +/- 12.2, and 5.19 +/- 0.5 mumoles/gm dry weight, respectively, p < 0.05). CONCLUSIONS: These alterations in high energy phosphate compounds in liver and skeletal muscle indicate that although the energy charge is maintained, energy depletion occurs early in the tumor-bearing state. These changes are tumor specific, not related to anorexia, and revert to non-tumor-bearing levels after tumor resection.

Adenosine Triphosphate↗

Isolated portal vein involvement in pancreatic adenocarcinoma. A contraindication for resection?

OBJECTIVE: This study was designed to examine the morbidity, mortality, and survival of patients undergoing portal vein resection (PVR) for adenocarcinoma of the pancreas. SUMMARY BACKGROUND DATA: Inability to separate the pancreas from the portal vein has historically been a locoregional contraindication for resection in patients with adenocarcinoma of the pancreas, and frequently, isolated local invasion of the portal veins is the only obstacle to curative resection. METHODS: A review of the prospective database for adenocarcinoma of the pancreas at Memorial Sloan-Kettering Cancer Center identified 332 patients who underwent pancreatic resection. Of those, 58 (17%) were identified as having isolated clinical involvement of the portal vein and underwent pancreatic resection with PVR. Patients undergoing curative pancreatic resection without PVR over this same time period comprise the control group. RESULTS: The 5% in-hospital mortality rate for PVR was not significantly different from that seen in those patients who did not undergo PVR (3%). Overall median survival for the PVR group was 13 months (range, < 1-109 months), which was not statistically different from those patients undergoing pancreatic resection without PVR (17 months (range, < 1-132 months). CONCLUSIONS: These results suggest that suspected isolated portal vein involvement should not be a contraindication for pancreatic resection in patients with adenocarcinoma.

Adenocarcinoma↗

Perioperative growth hormone improves wound healing and immunologic function in rats receiving adriamycin.

Administration of perioperative growth hormone may reverse alterations in wound healing and immunologic function in animals receiving chemotherapy. F344 rats were randomized into three groups: Control (n = 12), Chemo (n = 13), and Chemo + GH (n = 12). Human growth hormone (GH) (3 mg/kg sc bid) was begun on Day 0 and continued for 2 weeks. On Day 7, all animals underwent a standardized midline laparotomy, gastrotomy, and placement of a subcutaneous wound sponge. In addition, a single dose of adriamycin (5 mg/kg i.v.) was administered to those animals receiving chemotherapy. On Day 12, right hindlimb footpads were challenged with 50 micrograms of dinitrochlorobenzene. On Day 14, bursting strengths of the laparotomy and gastrotomy were measured. The wound sponge and gastric anastomosis were analyzed for hydroxyproline (OH-Pro) content. Animal spleens were weighed and splenocytes harvested for NK cell activity. Delayed type hypersensitivity (DTH) is reported as percentage of hind-limb foot pad swelling (%FPS). Data are expressed as means +/- SD and comparisons by ANOVA. The laparotomy bursting strength (mm Hg) in the Chemo + GH group (81 +/- 14) was significantly higher than that in the Chemo group (66 +/- 15, P < 0.05). The anastomotic tissue OH-Pro levels (mumole/g dry tissue) in the Chemo + GH group (107.9 +/- 15.2) were significantly higher than those in the Chemo group (62.9 +/- 8.5, P < 0.001). GH increased splenic weights (mg) over those of Chemo (0.50 +/- 0.13 vs 0.37 +/- 0.05, P < 0.05). NK cell activity (% killing) was significantly elevated in the Chemo+GH group compared to that in Chemo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Simultaneous measurement of local glucose utilization and blood flow in the rat brain: an autoradiographic method using two tracers labeled with carbon-14.

A simplified technique that uses two radionuclide tracers has been devised to measure local cerebral glucose utilization (ICGU) and local cerebral blood flow (ICBF) in the same rat. The method employs [14C]-2-deoxyglucose and [14C]iodoantipyrine to produce an autoradiogram before and another after extraction into chloroform of the [14C]iodoantipyrine from the brain sections. The chloroform-extracted autoradiogram yields ICGU, and the difference in tissue carbon-14 concentration between the two autoradiograms permits calculation of ICBF. The double-isotope technique provides values of ICGU and ICBF that are statistically indistinguishable from those derived from conventional single-isotope methods.

Animals↗