Squamous carcinoma of the head and neck in organ transplant recipients: Possible role of oncogenic viruses

A consistently increased incidence of malignancies in renal transplant recipients has been attributed to the effect of chronic immunosuppression required to prevent transplant rejection. Tumors arising in such patients offer a unique opportunity to study the interactions of the immune system and tumor development. A series of three cases of head and neck squamous cell carcinoma arising in patients after renal, cardiac, or bone marrow transplantation are reported. Patient ages at tumor diagnosis were 18, 29, and 53 years, respectively. Time from transplant to diagnosis of tumor ranged from 7 months to 12 years. Only the youngest patient lacked a history of exposure to the traditional predisposing factors of tobacco and alcohol use. Histo-pathologic examination in all three tumors showed features of koilocytosis with hyperkeratosis and parakeratosis suggestive of papillomavirus infection. Squamous carcinoma cells from one of these patients have been successfully established in cell culture. Immune system impairments secondary to the use of antirejection drugs could allow the expression of oncogenic viruses. A recent report of human papillomavirus (HPV) DNA in a primary and metastatic perianal squamous cell carcinoma from a renal transplant recipient, as well as the reported presence of HPV in benign and malignant neoplasms of the upper aerodigestive tract suggests that HPV infection could play a role in the development of squamous carcinomas in transplant recipients. Further studies of HPV invection in cultured cell lines derived from head and neck tumors occurring in immunosup-pressed patients are needed to define this relationship.     

Permanent constriction of the jaw due to idiopathic bilateral hyperplasia of the coronoid process]

Bilateral hyperplasia of the coronoid processes of the mandible is not frequent and concerns most always males between the ages of 14 and 16. The restricted opening movement is caused by impingement of the process on the medial and anterior surfaces of the zygomatic arch. The diagnostic is made by a good radiography. The treatment is surgery by intraoral approach. The coronoid processes are removed on the two sides with postoperative physiotherapy. The results are good and permanent.     

Acute and Subacute Polyhydramnios in Singleton Pregnancies

Over a 10-year period when 51,022 singleton infants were delivered, 19 pregnancies (1 in 2,685) were complicated by acute polyhydramnios 17 (1 in 3,000) by subacute polyhydramnios and 501 (1 in 102) by chronic polyhydramnios. The incidence of major congenital malformations in singleton pregnancies associated with acute polyhydramnios was 63% and the perinatal mortality rate was 74%. When subacute polyhydramnios occurred in singleton pregnancies, the incidence of major congenital malformations was 65%, similar to acute polyhydramnios, but the perinatal mortality rate was only 35%. The comparable figures for chronic polyhydramnios in singleton pregnancies were a major malformation incidence of 14% and perinatal mortality rate of 10%. The type of onset of polyhydramnios, acute, subacute or chronic is therefore the most important indicator of prognosis. In patients with gross polyhydramnios, acute renal failure must be specifically excluded.     

Hematologic toxicity during craniospinal irradiation: The impact of prior chemotherapy

The purpose of this work was to determine the frequency of hematologic toxicity during craniospinal radiation (CSI) and the impact of preirradiation chemotherapy on this frequency. The charts of 37 patients who received CSI were reviewed. Twenty did not have prior chemotherapy (CT—), while 17 did receive 1 to 18 (mean 5) cycles of multi-agent systemic chemotherapy (CT+). Leukopenia/thrombocytopenia necessitating treatment interruptions occurred in 1/20 (5%) in the CT— group, compared to 8/17 (47%) among the CT+ group. This difference was statistically significant, P < 0.0001 (Fisher's exact two-tailed test). The duration of treatment interruption in the CT+ patients was 4–24 days (mean 14). Compared to the CT— group, the CT+ group had a statistically significant greater decline in their white blood cell count (WBC), platelet count, and hematocrit (HCT) during CSI (percent reduction per Gy; (P = 0.018, 0.006, and 0.047, respectively). Although not statistically significant, the CT+ group also experienced lower nadir ratios (nadir count/baseline count) in terms of WBC and platelets (P = 0.07 and 0.22, respectively). While the mean pretreatment baseline blood counts were lower in the CT+ group compared to the CT— group, these differences reached statistical significance for the HCT (P = 0.02), but not the WBC (P = 0.59) or platelets (P = 0.43). Leukopenia and thrombocytopenia are very common in patients who receive craniospinal irradiation following multi-agent systemic chemotherapy. This appears to be due to more rapid and marked reductions in counts during CSI. Since this toxicity may cause treatment interruptions that are potentially therapeutically disadvantageous, aggressive hematologic support with transfusions and growth factors may be necessary. This problem may become more common as combined modality therapy is used more frequently. © 1995 Wiley-Liss, Inc.     

Acute Monocytic Leukemia: A Single Institution Experience

Using strict FAB criteria, 39 cases of monocytic leukemia were identified in 463 consecutive cases of AML. Patients had a median age of 49 with no sex predominance. Extramedullary disease and hyperleukocytosis were common (54% and 36% of patients respectively). Cytogenetic analysis was successful in 38 of 39 patients; 71% had a cytogenetic abnormality and 42% of these involved chromosome 11; 14 of 16 chromosome 11 abnormalities involved the region of 11q23. Non-chromosome 11 abnormalities tended to occur in older patients and to be associated with a lower platelet count; patients with the translocation 9;11 tended to have a lower white count and a higher incidence of therapy-related leukemia. 35 patients were treated with induction therapy including intensive chemotherapy (n = 33) and allogeneic BMT at presentation (n = 2). Patients who entered remission underwent consolidation chemotherapy, autologous BMT, or allogeneic BMT depending on policies at the time of diagnosis. Of 6 patients who underwent further intensive chemotherapy there is 1 long-term disease-free survivor. 3 of 8 patients undergoing autologous BMT and 2 of 3 patients undergoing allogeneic BMT are long-term disease-free survivors. We conclude that this specific subtype of AML, relatively rare when strict criteria are applied, is associated with unique biologic and clinical features and that the high relapse rate associated with conventional therapy makes new treatment approaches involving stem cell transplantation or immunomodulation necessary.     

Local delivery of the topoisomerase I inhibitor camptothecin sodium prolongs survival in the rat intracranial 9L gliosarcoma model

Camptothecin, a naturally occurring inhibitor of the DNA-replicating enzyme topoisomerase I, demonstrated promising anti-tumor activity in pre-clinical testing; however, because of unexpected toxicity and low anti-tumor effects in the initial clinical trials, further testing was discontinued. We hypothesized that local controlled delivery of camptothecin sodium would achieve effective concentrations in brain tumors without the observed systemic side effects, thereby allowing this novel drug to be used to treat patients with malignant gliomas. To test this hypothesis, we evaluated the sensitivity of rat glioma lines and established human glioma lines to camptothecin in vitro. We found that the LD₉₀ for the established rat and human lines was 0.3 to 1.4 μM after a 1 hr exposure and decreased to less than O.1 μM after continuous exposure for 7 days. We loaded camptothecin into a controlled-release polymer (ethylene-vinyl acetate co-polymer; EVAc) and showed by high-pressure liquid chromatography that controlled release occurred over at least 21 days. We then tested camptothecin against 9L gliosarcoma, implanted into the brain of Fischer 344 rats. Five days after tumor implantation, animals were treated with camptothecin delivered either systemically or locally by release from EVAc. Local controlled delivery by the polymer significantly extended survival: 59% of the treated animals were long-term survivors (> 120 days) compared to 0% of controls. Systemic administration did not extend survival compared to controls. We compared the efficacy of camptothecin delivered locally with a polymer to camptothecin injected directly into the tumor. Camptothecin increased survival only when delivered locally by polymer. © 1995 Wiley-Liss, Inc.     

A critical appraisal of impedance plethysmography in the diagnosis of acute deep venous thrombosis

Compulsive performance of the test is paramount to obtaining good results. Sequential multiple tests with prolongation of the filling time to maximize venous filling and ultimately reaching a plateau is essential. Increase in venous filling by increasing the cuff pressure in the proximal lower thigh occluding cuff to 60 instead of 45 centimeters of water is helpful in obtaining optimum venous filling. Unrecognized patient apprehension or muscle contraction may be a reason for false-positive IPGs. Patient relaxation, local heat application or even electromyography attachment may be helpful. The IPG can be repeated after a few hours if a false-positive test result is suspected. If a test falls above the stop line, the NPV is so high that no repetition of the test is necessary and the limb is read out as showing no proximal venous thrombosis. If a test is normal or borderline, the test may be repeated with sequential testing until the test points seem to group together or a clear divergence of either normal or abnormal is achieved. If the contralateral limb is clearly normal and an abnormal test result is obtained in the suspected limb, the test is likely to be reliable. Bilateral abnormal IPGs, especially in the presence of congestive heart failure or severe edema, may indicate a false-positive test finding. Increased edema in the extremity decreases electrical resistivity and balancing the machine may become a technical problem.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of infants with malignant gliomas: The Pediatric Oncology Group Experience

Although survivals of infants with malignant brain tumors are worse than any other age group, one possible exception to this rule are the malignant gliomas. Eighteen children less than 3 years of age with malignant gliomas (glioblastoma multiforme, anaplastic astrocytoma and malignant glioma) were treated on the Pediatric Oncology Group regimen of prolonged postoperative chemotherapy and delayed irradiation, (1986–1990). Of 10 children evaluable for neuroradiologic response, 6 had partial responses (> 50% reduction) to two cycles of cyclophosphamide and vincristine. Progression free survivals at l, 3 and 5 years were 54.25% ± 12, 43% ± 16 and 43% ± 23 respectively. Survivals at 5 years were 50% ± 14. Four children were not irradiated after 24 months of chemotherapy due to parental refusal and none have developed recurrent disease. Neither degree of surgical resection, presence or absence of metastases, nor pathology influenced survival but this may reflect small sample size. This study suggests that some malignant gliomas in infants are chemotherapy sensitive and may be associated with a good prognosis. Why infants with these high-grade gliomas fare better than adults is not clear. It is likely that there is something intrinsically different about them that cannot be identified on routine pathologic examination.     

Trifluoperazine as a modulator of multidrug resistance in refractory breast cancer

 Overexpression of P-glycoprotein (P-gp) has been implicated as the mechanism of multidrug resistance (MDR) in a number of human cancers, including carcinoma of the breast. We conducted a clinical trial to determine whether the P-gp inhibitor, trifluoperazine, could sensitize patients with refractory breast cancer to vinblastine chemotherapy. Adult patients with histologically confirmed, refractory, advanced breast cancer were treated with vinblastine at a dose of 1.7 mg/m² per day by continuous infusion for five consecutive days. Patients who did not respond after two cycles were subsequently treated with vinblastine plus trifluoperazine at a dose of 8 mg twice daily during the five days of chemotherapy. In patients from whom tumor samples were available, the expression of P-gp was determined by immunocytochemistry. Of 35 patients enrolled, 30 were evaluable, 2 of whom (7%) achieved a partial response to vinblastine alone. Among the 16 patients treated with vinblastine plus trifluoperazine there was one response (6%) which lasted 16 weeks. Tumor samples were available from 16 patients, and 14 (87%) were immunoreactive for P-gp. P-gp expression was detected both in the patient who responded to vinblastine plus trifloperazine and in one of the two patients who responded to vinblastine alone. Continuous-infusion vinblastine demonstrated limited activity in this study. Furthermore, trifluoperazine did not effectively reverse established resistance to vinblastine. This failure may be related the presence of multiple mechanisms of drug resistance in this heavily pretreated population, or because ineffective concentrations of the modulator were achieved in vivo. Future studies should evaluate more effective modulators, and attempt to reverse MDR earlier in the course of treatment, before other forms of resistance can develop. Received: 12 January 1995/Accepted: 11 August 1995