The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies

The objective of this study was to examine the effects of the intakeof dietary fat upon colorectal cancer risk in a combined analysis of datafrom 13 case-control studies previously conducted in populations withdiffering colorectal cancer rates and dietary practices. Original datarecords for 5,287 cases of colorectal cancer and 10,470 controls werecombined. Logistic regression analysis was used to estimate odds ratios (OR)for intakes of total energy, total fat and its components, and cholesterol.Positive associations with energy intake were observed for 11 of the 13studies. However, there was little, if any, evidence of anyenergy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01,1.02, and 0.92 for quintiles of residuals of total fat intake (P trend =0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (Ptrend = 0.39). The analysis suggests that, among these case-control studies,there is no energy-independent association between dietary fat intake andrisk of colorectal cancer. It also suggests that simple substitution of fatby other sources of calories is unlikely to reduce meaningfully the risk ofcolorectal cancer.     

Percutaneous gastrostomy tube placement in patients with ventriculoperitoneal shunts

Objective. The purpose of this study is to determine the risk of CNS and/or peritoneal infection in children with ventriculoperitoneal shunts in whom a percutaneous gastrostomy tube is placed. Materials and methods. We placed 205 gastrostomy or gastrojejunostomy tubes from January of 1991 to December 1996. Twenty-three patients (10 boys, 13 girls) had ventriculoperitoneal shunts at the time of placement. All shunts were placed at least 1 month prior to placement of the gastrostomy tube. The patients ranged in age from 8 months to 16 years with a mean age of 6 years, 9 months. Patient weight ranged from 2 kg to 60 kg. All 23 children required long-term nutritional support due to severe neurologic impairment. No prophylactic antibiotics were given prior to the procedure. Of the patients, 21/23 had a 14-F Sacks-Vine gastrostomy tube with a fixed terminal retention device inserted, using percutaneous fluoroscopic antegrade technique. Two of the 23 patients had a Ross 14-F Flexi-flo gastrostomy tube which required a retrograde technique due to a small caliber esophagus in these children. Results. All 23 children had technically successful placements of percutaneous gastrostomy (7) or gastrojejunostomy (16) tubes. Of the children, 21/23 (91 %) had no complications from the procedure. Two of 23 (9 %) patients demonstrated signs of peritonitis after placement of their gastrostomy tubes and subsequently had shunt infections. In both, children CSF culture grew gram-positive cocci. The antegrade technique was used in both children who developed peritonitis. Conclusion. Our study indicates children with ventriculoperitoneal shunts who undergo percutaneous gastrostomy are at greater risk for infection and subsequent shunt malfunction. Therefore, we recommend prophylactic antibiotic therapy to cover for skin and oral flora. Received: 5 August 1997 Accepted: 26 December 1997     

Epstein-Barr Virus Polymerase Chain Reaction and Serology in Pediatric Post-Transplant Lymphoproliferative Disorder: Three-Year Experience

To assess whether the semiquantitative peripheral blood Epstein-Barr virus (EBV) polymerase chain reaction (PCR) test correlates with post-transplant lymphoproliferative disorder (LPD), we compiled the results of the test done over a 3-year period ending July 1997. Six hundred seventy-six tests were done on 185 patients. Four hundred-thirty tests (63%) were negative, 167 (25%) were weak positive, 67 (10%) were moderate positive, and 12 (2%) were strong positive. Twelve of the patients developed a lymphoproliferative disorder (LPD) during this time. The EBV PCR tests proximate to the diagnosis of LPD in the 12 patients with EBV-positive LPD were 6 strong positive, 5 moderate positive, 1 weak positive. No patient with LPD had a negative result at diagnosis. Stated another way, 6/12 (50%) of strong-positive PCR tests, 5/67 (7%) moderate-positive tests, and 1/167 (.6%) of weak-positive tests correlated with LPD. Serologic evaluation for EBV done on 7 patients at the time of LPD showed low serologic responses in 5 of the 7 patients. The EBV PCR temporally associated with the serology indicated moderate to large viral burdens. In each patient evaluated serially, the EBV PCR test rose before the diagnosis of LPD and fell with treatment for the disorder. In conclusion, the EBV PCR test may be used as an adjunct to the diagnosis of patients with LPD and may be used to monitor response to therapy for the disorder. Received August 26, 1997; accepted January 13, 1998.     

Determinants of tissue estradiol levels and biologic responsiveness in breast tumors

Estradiol stimulates the growth of breast tumor cells in both pre- and post menopausal women. Following the menopause, the levels of estradiol in breast tumor tissues are similar to those from tumors obtained prior to cessation of ovarian function, even though plasma estrogen levels are 10–50 fold lower in post- than in premenopausal women. These observations suggested the possibility of enhanced estradiol uptake from plasma or in situ synthesis in post-menopausal women. We systematically studied these possibilities in a series of model systems. Initially we demonstrated a very high affinity estradiol binding site in tissues from castrated rats. Enhanced uptake occurred under conditions of low plasma estrogen levels when compared to animals with higher estradiol levels. In situ synthesis also occurred both through the sulfatase and aromatase pathways. In further studies, we compared uptake from plasma with in situ synthesis via aromatase in a nude mouse model. Under the conditions utilized, in situ synthesis resulted in much higher tissue estradiol levels and tumor growth rates than did uptake from plasma. During these studies we demonstrated that tumors deprived of estradiol developed mechanisms rendering them more sensitive to estrogen. This involved the ability of cells to adapt to estradiol deprivation to allow them to be responsive to four log lower amounts of estrogen than when studied under wild type conditions. In addition, cells adapted by increasing their level of aromatase and thus developing the capability to become more sensitive to estrogen precursors. Taken together, these studies demonstrate that breast cancer tissue is highly plastic and can adapt to conditions of estrogen deprivation via a variety of mechanisms.     

Efficacy of Intravenous Granisetron to Control Nausea and Vomiting During Multiple Cycles of Cisplatin-Based Chemotherapy

The safety and efficacy of granisetron (10 µg/kg and 40 µg/kg) were evaluated during a second (n = 393) and third (n = 200) cycle of chemotherapy in this multicenter, double-blind, randomized, parallel-group study. Granisetron was administered as a single intravenous dose before the start of cisplatin chemotherapy (≥60 mg/m²). Total control (no vomiting, no retching, no nausea, and no use of antiemetic rescue medication) after the first 24 hr following chemotherapy was achieved in 40% and 49% of patients in Cycles 2 and 3, respectively, for the 10 µg/kg group, and in 42% and 38% of patients in Cycles 2 and 3, respectively, for the 40 µg/kg group. Both dose levels of granisetron were well tolerated. The results demonstrate comparable efficacy between the 10 µg/kg and 40 µg/kg doses of granisetron in preventing nausea and vomiting during repeat cycles of high-dose cisplatin-based chemotherapy. The results of this study show that granisetron 10 µg/kg is safe and well tolerated, and remains effective with repeat cycle use.     

Iatrogenic seeding of anaplastic astrocytoma following stereotactic biopsy

We present a case of probable tumor seeding along the needle tract following computer tomography-guided stereotactic biopsy of an anaplastic astrocytoma in a 23 year old male. Six months after the initial biopsy and 3 months following a second stereotactic procedure for cyst aspiration, a second lesion appeared directly along the biopsy trajectory at a distance from the primary tumor. This lesion is presumed to be recurrent tumor and appears to have been spread iatrogenically following the biopsy of the initial tumor and the subsequent cyst aspiration along the same tract.     

Analysis of the p21 gene in gliomas

The p21 gene encodes a cyclin dependent kinase inhibitor protein (p21) which has a tumor suppressive activity in a variety of tumor cell lines. Since, the p21 gene is up-regulated by the p53 tumor suppressor gene, which is frequently mutated in gliomas, acting therefore in the same control pathway, it constitutes a good candidate gene to be also inactivated in these tumors. To test this hypothesis, DNAs from 81 gliomas (48 glioblastomas, 11 anaplastic astrocytomas, 10 low-grade astrocytomas, 12 oligodendrogliomas and mixed gliomas), were investigated for mutations in the p21 coding sequence by denaturant gradient gel electrophoresis followed by sequencing. All these tumors have been previously screened for p53 mutations. Three different DNA variants were identified on codon 31 (17 cases), 27 (1 case) and 117 (1 case) and shown to be also present in matching constitutional DNA, suggesting they were polymorphisms. None of the tumors demonstrated a somatic mutation. No significant correlation between the presence of a p21 variant and the p53 mutation tumor status was observed. In conclusion, mutation in the p21 gene unlikely contributes to the development of gliomas.     

A therapeutic trial of radiation therapy with Vincristine,etoposide, and Procarbazine (VVP) in high grade intracranial gliomas

This study is a combined modality Phase II therapeutic trial to determine the efficacy of the novel combination of VP-16, Vincristine and Procarbazine in addition to postoperative radiation therapy in patients with high grade intracranial gliomas. Thirty three patients (median age 51 years) were entered (27 with glioblastoma multiforme, 6 with anaplastic astrocytoma). Toxicity was manageable with no lethal toxicities. Five of seven life threatening toxicities were hematologic. Median overall survival was 14.2 months. These data suggest this regimen is effective treatment for patients with high grade gliomas.     

Dietary factors and the risk of squamous cell esophageal cancer among black and white men in the United States

Objectives: To investigate dietary factors for squamous cell esophageal cancer and whether these factors may contribute to the five-fold higher incidence of this cancer in the black versus white population of the United States.Methods: Data from a food frequency questionnaire were analyzed for 114 white men and 219 black men with squamous cell esophageal cancer, and 681 white and 557 black male controls from three areas of the United States who participated in a population-based case-control study of esophageal cancer.Results: Protective effects were associated with intake of raw fruits and vegetables (odds ratio for high versus low consumers=0.3 in both white and black men) and use of vitamin supplements (especially vitamin C; odds ratio for high versus low consumers=0.4 in both races), with the frequency of consumption of raw fruits and vegetables and vitamin supplements being greater for white than black controls. In addition, elevated risks were associated with high versus low intake of red meat (OR=2.7 for blacks and 1.5 for whites) and processed meat (OR=1.6 for blacks and 1.7 for whites), with the levels of consumption being greater for black than white controls.Conclusions: In the United States, these dietary factors may contribute in part to the much higher incidence of squamous cell esophageal cancer among black compared to white men.     

Postoperative adjuvant radiotherapy and 5-fluorouracil chemotherapy for rectal carcinoma

Postoperative combined modality therapy with radiotherapy and 5-fluorouracil (5FU) chemotherapy is an effective adjuvant approach that reduces locoregional and distant metastatic disease in patients with high-risk rectal carcinoma. However, this approach results in a treatment regimen of at least 6 months’duration. The present prospective study investigates the integration of radiotherapy and 5FU chemotherapy in a protocol designed to minimize toxicity and reduce the overall treatment time. A total of 40 patients with TNM stage II or III disease received postoperative radiotherapy at four fractions per week with weekly 5FU bolus injections delivered on the fifth non-radiotherapy day. Patients also received systemic chemotherapy with leucovorin both before and after pelvic irradiation, with the total treatment duration extending for only 18 weeks. Patients were able to complete radiotherapy in 90% of cases, while the delivery of full-dose chemotherapy was achievable in the vast majority. The incidence of haematologic and gastrointestinal toxicities requiring the cessation of treatment was acceptable. With a median follow-up of 20.9 months among surviving patients, the estimated progression-free and overall survival at 2 years were 71 % and 79%, respectively.