Chemotherapy for desmoid tumours in association with familial adenomatous polyposis: a report of three cases

Objective

To determine the efficacy of chemotherapy for inoperable desmoid tumours associated with familial adenomatous polyposis.

Design

A review of three cases of unresectable desmoid tumours and of the literature on the subject.

Setting

The Steven Atanas Stavro Polyposis Registry at Mount Sinai Hospital in Toronto.

Patients

Three patients with symptomatic, unresectable desmoid tumours associated with familial adenomatous polyposis and unresponsive to conventional hormone therapy.

Intervention

A chemotherapy regimen of seven cycles of doxorubicin (dose ranging from 60 to 90 mg/m²) and dacarbazine (1000 mg/m²), followed by carboplatin (400 mg/m²) and dacarbazine.

Outcome Measures

Clinical improvement and tumour regression demonstrated by computed tomography.

Results

In each of the three cases significant tumour regression was seen clinically and radiologically.

Conclusions

Cytotoxic chemotherapy is an effective treatment for desmoid tumours associated with familial adenomatous polyposis. The chemotherapy should be started early in cases of symptomatic desmoid tumour unresponsive to conventional medical therapy.     

Free fatty acid mobilization and oxidation during total parenteral nutrition in trauma and infection.

Free fatty acid (FFA) metabolism was studied in 18 traumatized and/or septic patients. Each patient was studied while receiving 5% dextrose (D5W) and after 4 to 7 days of total parenteral nutrition (TPN). Nonprotein energy during TPN was given either entirely as glucose (Glucose System) or as equal portions of intravenous fat and glucose (Lipid System). Plasma FFA concentrations were in the normal range on D5W and decreased markedly with TPN. FFA turnover was higher than normal on D5W and did not decrease significantly with TPN. The poor correlation between these two variables emphasizes the need to perform kinetic studies to characterize FFA metabolism in trauma and sepsis. Plasma FFA oxidation and net whole body fat oxidation measured by indirect calorimetry were in the normal range on D5W, 35 and 82%, respectively, of resting energy expenditure (REE). With a glucose intake averaging 108% of REE, plasma FFA oxidation and net fat oxidation decreased to 17 and 13%, respectively, of REE. Nonprotein RQ increased only to 0.94 despite administration of glucose in excess of REE, indicating an abnormal persistence of fat oxidation. During D5W administration, plasma FFA accounted for less than one half of total fat oxidation, indicating that unlabeled fat, such as tissue or plasma triglycerides not in rapid equilibrium with plasma FFA, accounted for the bulk of fat oxidation. Glucagon concentrations which were high on D5W did not decrease significantly with TPN. Insulin concentrations were normal on D5W and increased in response to TPN. The abnormal hormonal milieu may account for much of the abnormal fat metabolism. Administration of large amounts of glucose decreased FFA oxidation much more than FFA mobilization. Thus, the infused glucose acts to increase the rate of "futile cycling" of FFA in these acutely ill patients.     

X-Ray Structure and Crystal Lattice Interactions of the Taxol Side-Chain Methyl Ester

A colorless, parallelepiped crystal of methyl (2R,3S)-N-benzoyl-3-phenylisoserinate belonging to the space group P2_l with a = 5.414(4), b = 7.813(1), c = 17.802(7) , = 90.87(4)°, Z = 2, V = 752.9 ³, D _calc = 1.32 g cm^–3, and µ_calc = 1.02 cm^–1 was selected and the structure solved using direct methods. Refinement led to a final R = 0.079 for 819 [F _o 5(F_o)] reflections. Intermolecular hydrogen-bonding interactions are prevalent in the crystal lattice of this compound.     

Interrelationship between retinal ischaemic damage and turnover and metabolism of putative amino acid neurotransmitters,glutamate and GABA

Conditions causing a reduction of oxygen availability (anoxia), such as stroke or diabetes, result in drastic changes in ion movements, levels of neurotransmitters and metabolites and subsequent neural death. Currently, there is no clinically available treatment for anoxia induced neural cell death resulting in drastic and permanent central nervous system dysfunction. However, there have been some exciting developments in experimentally induced anoxic conditions where several classes of drugs appear to significantly reduce neural cell death. This report aims to provide the foundations for understanding both the basic mechanisms involved in retinal ischaemic damage and experimental treatments used to prevent such damage. We discuss the normal release, actions and uptake of the fast retinal neurotransmitters, glutamate and GABA, in the vertebrate retina. Immunocytochemistry is used to demonstrate that both glutamate and GABA are found in the macaque retina. Following this is a discussion on how ischaemia may enhance neurotransmitter release or disrupt its uptake, thus causing an increase in extracellular concentration of these neurotransmitters and subsequent neuronal damage. The mechanisms involved in glutamate neurotoxicity are reviewed, because excess glutamate is the likely cause of retinal ischaemic damage. Finally, the mechanisms behind four possible modes of treatment of neurotransmitter toxicity and their advantages and disadvantages are discussed. Hopefully, further research in this area will lead to the development of a rational therapy for retinal, as well as cerebral ischaemia.Abbreviations -KG -ketoglutarate - AAT aspartate amino transferase - AC amacrine cell - ACL amacrine cell layer - BC bipolar cell - CNS central nervous system - EAA excitatory amino acids - G'ase glutaminase - GABA -amino butyric acid - GABA-T GABA transaminase - GAD glumatic acid decarboxylase - GC ganglion cell - GCL ganglion cell layer - GDH glutamate dehydrogenase - gj gap junction - GS glutamine synthetase - HC horizontal cell - ILM inner limiting membrane - INL inner nuclear layer - IPC inter-plexiform cell - IPL inner plexiform layer - IS inner segment of photoreceptor - NFL nerve fibre layer - NMDA N-methyl-D-aspartate - OLM outer limiting membrane - ONL outer nuclear layer - OPL outer plexiform layer - OS outer segment of photoreceptor - Ox acetateoxaloacetate - RL receptor layer - SSAD succinate semi-aldehyde decarboxylase - Succinate SA succinate semi aldehyde - TCA cycle tricarboxylic acid cycle     

Introduction of bias in residency-candidate interviews

We have developed, as part of our resident applicant ranking process, a computerized weighted scoring system incorporating, among other variables, the interview score (IS). This study was undertaken to test the IS as a dependent variable when the applicant file is available during the interview. Over a 3-year period, each of two faculty members interviewed 133 candidates in a "blinded" fashion (file unavailable) or 290 candidates with an "open" file. The mean discrepancy between paired interviewers (1 to 10 scale) was 1.34 +/- 0.10 for the blinded group versus 0.93 +/- 0.06 for the open group (p less than 0.001). Individual and multiple regression analysis were used to test the IS as a dependent variable in the open group, with the blinded group as a control. In each instance (except clerkship grades), the IS correlated more closely with other parameters (p less than 0.05) in the open group. Correlation coefficients were 0.27 (blinded) and 0.64 (open) for weighted scores combining all parameters (p less than 0.001) and 0.39 (blinded) and 0.65 (open) for multiple linear regression analysis (p less than 0.001). We conclude that the IS is significantly influenced if other objective variables are at hand, thus deflating the actual weight of the interview. To accurately quantify the value of the interview, a correction factor must be applied, or, more appropriately, the interview must be conducted blindly.     

The types of heterosexual gender identity disorder

The rationale for dividing the clinical spectrum of DSM-III-R male heterosexual gender identity disorder into three types was examined. The DSM-III-R category of fetishism for female attire, was included in the analysis. There were 266 male participants divided into three groups: 172 fetishists for female attire or gender identity patients, 52 androphiles, and 42 gynephiles. A 16 item questionnaire was used to examine the groups. A three factor scale ("Fetishism", "Gender Dysphoria" and "Androphilia") was derived from the questionnaire. Only the Gender Dysphoria Factor Scale successfully differentiated between all four conditions, supporting the notion that the three types of gender identity disorder represent a continuum of degree of severity of gender dysphoria. Defining two of the three types of gender identity disorder in terms of the patients' self-reports on fetishism, as DSM-III-R does, is therefore unnecessary.     

Human autologous tumor-specific T-cell responses induced by liposomal delivery of a lymphoma antigen.

PURPOSE: The idiotype (Id) of the immunoglobulin on a given B-cell malignancy is a clonal marker that can serve as a tumor-specific antigen. We developed a novel vaccine formulation by incorporating Id protein with liposomal lymphokine that was more potent than a prototype, carrier-conjugated Id protein vaccine in preclinical studies. In the present study, we evaluated the safety and immunogenicity of this vaccine in follicular lymphoma patients. EXPERIMENTAL DESIGN: Ten patients with advanced-stage follicular lymphoma were treated with five doses of this second generation vaccine after chemotherapy-induced clinical remission. All patients were evaluated for cellular and humoral immune responses. RESULTS: Autologous tumor and Id-specific type I cytokine responses were induced by vaccination in 10 and 9 patients, respectively. Antitumor immune responses were mediated by both CD4+ and CD8+ T cells, were human lymphocyte antigen class I and II associated, and persisted 18 months beyond the completion of vaccination. Specific anti-Id antibody responses were detected in four patients. After a median follow-up of 50 months, 6 of the 10 patients remain in continuous first complete remission. CONCLUSIONS: This first clinical report of a liposomal cancer vaccine demonstrates that liposomal delivery is safe, induces sustained tumor-specific CD4+ and CD8+ T-cell responses in lymphoma patients, and may serve as a model for vaccine development against other human cancers and infectious pathogens.     

Vascular compression of the airway: Indications for and results of surgical management

Vascular compression of the airway is a significant cause of respiratory compromise in children. While the indications for surgical repair are sometimes life threatening, they can also be subtle. This retrospective study examines 45 surgical cases of tracheobronchial compromise secondary to vascular compression at a large children's hospital between July 1983 and February 1996. A total of 34 were diagnosed with innominate artery compression, ten with a double aortic arch and one with an anomalous right subclavian artery. The 45 patients, 25 male and 20 female, ranged in age from 12 days to 11 years at surgery (average 13 months). A total of 21 (47%) presented with proven or suspected episodes of cyanosis or apnea. All 45 patients had evidence of vascular compression during microlaryngoscopy and bronchoscopy. The diagnosis was confirmed by magnetic resonance imaging (MRI) in 23/45 (51%), barium swallow in 22/45 (49%) and aortogram in 3/45 (7%). There was one death. One patient had a tracheotomy before surgery and continues to require it after surgery. Complete resolution of symptoms was achieved in 39/45 (87%) with five requiring more than one operation before their symptoms resolved completely. A total of four patients experienced a recurrence of symptoms within a variable length of time after surgery. Surgical indications and treatment alternatives will be discussed.     

Peripheral progesterone (P) levels and endometrial response to various dosages of vaginally administered P in estrogen-primed women

Objective: To compare the pharmacokinetics and pharmacodynamics of 100 mg/d, 200 mg/d, and 400 mg/d (200 mg two times per day) of P administered vaginally for 14 days to estrogen-primed postmenopausal women.Design: Randomized, open-label, three-way crossover study.Setting: Two university-based investigative sites.Patient(s): Twenty healthy postmenopausal women with histologically normal endometria.Intervention(s): Oral 17,β-E₂ was given each day of a 28-day cycle; a P vaginal suppository was inserted daily according to the randomization schedule during days 15–28 of each cycle; blood samples were collected; an endometrial biopsy was obtained on day 25; and patients were crossed over to the next treatment cycle after a washout period of at least 30 days.Main Outcome Measure(s): Mean P blood levels, endometrial dating/conversion.Result(s): There was good vaginal absorption of P for all dosages. Endometrial conversion occurred in all 200- and 400-mg/d P-dosed cycles, whereas the 100-mg/d dosage failed to convert primed endometria consistently. There also was a significantly increased tendency for earlier bleeding and spotting with the 100-mg/d dosage.Conclusion(s): Both the 200- and 400-mg/d dosage regimens consistently convert an estrogen-primed endometrium, and yield appropriate endometrial dating and bleeding patterns. However, the 400-mg/d dosage attains the highest sustained blood levels and may be the best dosage regimen for further study.     

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