Phase II study of combination human recombinant GM-CSF with intermediate-dose cytarabine and mitoxantrone chemotherapy in patients with high-risk myelodysplastic syndromes (RAEB, RAEBT, and CMML): an Eastern Cooperative Oncology Group Study.

A Phase II study of GM-CSF with intermediate-dose cytarabine and mitoxantrone was conducted in patients with high-risk myelodysplastic syndrome. It was designed to evaluate if priming with growth factor could increase the efficiency of chemotherapy. In this older population only two of 10 patients achieved a bone marrow CR, including one patient whose leukemic blasts had an "S" phase increase of 2.55x at 48 hr. Unexpected hepatotoxicity was noted. This regimen cannot be recommended for this elderly population of patients.

Conservative treatment of rectal adenocarcinoma.

Endocavitary radiotherapy and transrectal excision are highly effective treatments for properly selected patients with favorable early-stage rectal adenocarcinoma. The likelihood of local control and survival after treatment with either modality is similar, and differences among various series probably reflect selection. The parameter most predictive of local control and survival in the authors' series was tumor configuration. As has been previously observed, "selection is the silent partner of success." Suitable candidates for endocavitary radiotherapy or wide local excision are patients whose tumors are 3 cm or less in diameter, well-to-moderately differentiated, exophytic, mobile, limited to the submucosa on transrectal ultrasound, and within 10 cm of the anal verge. The advantages of endocavitary irradiation are (1) it is an outpatient procedure, (2) it does not require anesthesia, and (3) it is less expensive than transrectal excision. The advantages of transrectal excision are (1) it may be performed during one brief hospitalization (as opposed to four outpatient visits), and (2) a small subset of patients will have pathologic findings predicting an increased risk of regional lymph node involvement, revealing the need to treat the nodes with external-beam radiotherapy. A disadvantage of wide local excision is that some patients who would be suitable for a local procedure alone must be subjected to a course of external-beam radiotherapy when they are found to have equivocal or positive margins. Patients who are treated with transrectal excision and external-beam radiotherapy have less favorable lesions and are not comparable with patients who are treated with endocavitary radiotherapy or wide local excision alone. They are best compared with patients who have undergone major surgery consisting of abdominoperineal resection or low anterior resection. Because the risk of positive nodes is significantly increased with adverse pathologic findings such as poor differentiation, invasion of the muscularis propria, and endothelial-lined space invasion, a subset of these patients treated with wide local excision would have positive nodes. This subset of patients is not comparable with patients with stage pT1N0 and pT2N0 tumors treated with major surgery. The latter group of patients undergo complete surgical staging, whereas the pathologic staging for patients who undergo wide local excision and radiotherapy is limited to the extent of the primary tumor. With this caveat in mind, wide local excision and radiotherapy seem to result in locoregional control and survival rates similar to the rates obtained with major surgery for patients with pT1 and pT2 cancers (Table 5). Patients who should receive postoperative irradiation have tumors that exhibit one or more of the following characteristics: size greater than 3 cm in diameter, poorly differentiated, invasion of the muscularis propria, endothelial-lined space invasion, fragmented resection, equivocal or positive margins, or perineural invasion. Patients with gross residual disease are not suitable candidates for radiotherapy and require further surgery. The authors' policy is to treat these patients with chemoradiation followed by resection. Patients thought to have transmural invasion before treatment are probably best treated with preoperative chemoradiation combined with major surgery, although a subset of patients can be downstaged and rendered suitable for a wide local excision.

Distant cancer effects on standardised testing of peripheral vision.

BACKGROUND: Profound central-retinal visual losses have been a major presenting factor reported in cancer and melanoma associated retinopathies (CAR, MAR). However, it is well established that standardised tests of peripheral retinal function are often the most sensitive detectors of early eye disease. This is a preliminary investigation of the responsiveness of the peripheral retina to "distant" (non-eye or CNS) cancers using easily obtained standardised tests. METHODS: The design is a single blind study where test results are compared with published norms and a small age matched control group. Of 120 ambulatory cancer outpatients who were interviewed at routine follow up examinations, 111 volunteered and admitted a range of mild visual changes. 25 cancer patients completed all tests of peripheral vision function and a clinical screening. There were seven control subjects of the same age range. RESULTS: 98% (49 of 50) of eyes from the patient cohort were judged clinically normal following examinations which emphasised the central retina, fundus appearance, and static fields. On testing which emphasised the visual periphery, 46 (92%) eyes showed one or more quantitative abnormalities >2 SD from the age adjusted norm means. These abnormalities clustered mainly about dark adaptation (rod cell) sensitivity (31, 62% of measured sites), the blue sensitive retinal cells (17, 34% of measured eyes), and the oscillatory component (OP) of the electroretinogram (23, 46% of measured eyes). One control eye (7%) showed a significant dark adaptation abnormality and ERG reduction. There was no identifiable interaction between chemotherapy mode and the cancer associated retinal deficits (CARD). Antiretinal antibodies were found in sera from most patients and controls. CONCLUSION: CARD is common in the retinal periphery of many cancer patients, and is distinct from rare CAR, MAR central-retinal responses. CARD has numerous potential clinical uses which justify expanded research with more defined large samples.

Primary primitive neuroectodermal tumor of the kidney. Case report and review of the literature.

Small cell tumors are a heterogeneous group of neoplasms with similar morphologic features. They include lymphomas, carcinomas with variable degrees of neuroendocrine differentiation, rhabdomyosarcomas, and neuroblastomas. The authors describe a rare case of primitive neuroectodermal tumor (PNET) located in the kidney that was thoroughly studied with modern diagnostic techniques, including expression of protein P 30/32 MIC2 with the antibody 013 with subsequent demonstration of a genetic translocation consistent with t(11;22). The literature on small cell tumors of the kidney, with special emphasis on PNET, is reviewed.

Preoperative treatment of patients with locally advanced unresectable rectal adenocarcinoma utilizing continuous chronobiologically shaped 5-fluorouracil infusion and radiation therapy.

BACKGROUND: This study was designed to determine the efficacy and maximally tolerated dose of 5-fluorouracil when administered by chronobiologically shaped prolonged infusion in combination with radiation therapy in patients with both locally advanced and unresectable rectal carcinoma. METHODS: Eighteen sequential patients determined clinically to have either locally advanced or unresectable rectal carcinoma were treated by 4500 centigray (cGy) or 5580 cGy, respectively, combined with continuous chronobiologically modulated 5-FU infusion starting at 250 mg/m2/day, with the dose escalating in each cohort of 5 patients if no Grade 3 or higher toxicity was observed in each cohort. Imaging studies were obtained prior to and after completion of treatment. RESULTS: All 18 patients completed the full course of radiation therapy and all were subsequently resectable for potential cure. The maximum tolerated dose of 5-FU was 275/m2/day for 5 weeks. Seven patients had a sphincter-sparing procedure, and ten patients underwent an abdominoperineal resection, all with clear margins. Five complete pathologic responses (28%) were obtained. The average follow-up time was 12 months with a range of 6 to 37 months. With the exception of two patients, one of whom declined surgery and one of whom died of widespread disease, all of the patients have remained free of disease. CONCLUSIONS: The combination of radiation therapy and continuous chronobiologically shaped 5-FU infusion at a dose of up to 275/m2/day is well tolerated and appears to be more effective in downsizing and possibly downstaging locally advanced and unresectable rectal carcinoma than radiation therapy alone. Longer follow-up will determine whether ultimate disease free and overall survival are improved by this method.

Placental metastasis from primary ocular melanoma: a case report.

Ocular malignant melanoma, similar to the cutaneous variety, may metastasize to the placenta, almost always in the presence of widespread disease. The prognosis is poor, and there is a 25% risk of spread to the fetus. All women with a history of this disease should be informed of the risks when they are contemplating pregnancy.

Radioreceptor binding profile of the atypical antipsychotic olanzapine.

The affinities of olanzapine, clozapine, haloperidol, and four potential antipsychotics were compared on binding to the neuronal receptors of a number of neurotransmitters. In both rat tissues and cell lines transfected with human receptors olanzapine had high affinity for dopamine D1, D2, D4, serotonin (5HT)2A, 5HT2C, 5HT3, alpha 1-adrenergic, histamine H1, and five muscarinic receptor subtypes. Olanzapine had lower affinity for alpha 2-adrenergic receptors and relatively low affinity for 5HT1 subtypes, GABAA, beta-adrenergic receptors, and benzodiazepine binding sites. The receptor binding affinities for olanzapine was quite similar in tissues from rat and human brain. The binding profile of olanzapine was comparable to the atypical antipsychotic clozapine, while the binding profiles for haloperidol, resperidone, remoxipride, Org 5222, and seroquel were substantially different from that of clozapine. The receptor binding profile of olanzapine is consistent with the antidopaminergic, antiserotonergic, and antimuscarinic activity observed in animal models and predicts atypical antipsychotic activity in man.

Current management of squamous cell carcinoma of the anal canal.

The management of squamous cell carcinoma of the anal canal is controversial. Treatment currently varies from abdominoperineal resection to combined radiotherapy and chemotherapy. Our aim is to review the management of this disease and present our current treatment policies. Twenty-six patients treated at the University of Florida with surgery and adjuvant radiotherapy are compared with 12 patients treated with radiotherapy alone. The pertinent literature is reviewed to determine the role of primary surgery, the efficacy of adjuvant chemotherapy, and the optimal chemotherapy schedule. The preferred management of anal canal cancer is radiotherapy; abdominoperineal resection should be reserved for salvage after local recurrence and for patients with faecal incontinence caused by the destruction of the sphincter muscle. Adjuvant chemotherapy is probably indicated for patients with lesions that are stage T2 or larger. The optimal chemotherapy regimen consists of 5-fluorouracil and mitomycin. Preliminary data suggest that cisplatin may be substituted for mitomycin with equivalent efficacy and less toxicity.

Results of multimodality therapy for inflammatory breast cancer: an analysis of clinical and treatment factors affecting outcome.

This is a retrospective analysis of 50 patients with a minimum 2-year follow-up who had clinical signs and/or histologic evidence of inflammatory breast cancer and were treated with curative intent between October 1964 and March 1989. The 5-year relapse-free, absolute, and cause-specific survival rates for the overall group of 50 patients were 36, 39, and 45 per cent, respectively. Patients who received treatment with radiotherapy, chemotherapy, and surgery (n = 33) had a 5-year relapse-free survival rate of 50 per cent, compared with 7 per cent for those patients (n = 17) who received less treatment (P = 0.0002). The only clinical factor with a negative impact on relapse-free survival was mass size > 5 cm (P = 0.07). No advantage could be demonstrated for preoperative chemotherapy over postoperative chemotherapy or for doxorubicin-containing regimens over cyclophosphamide, methotrexate, and 5-fluorouracil. There was no difference in the incidence of distant metastases for patients receiving preoperative rather than postoperative chemotherapy, but there were more local recurrences in patients in whom local-regional treatment was delayed. A higher rate of arm edema was associated with more extensive surgery.

Gaucher's disease associated with chronic lymphocytic leukemia.

To date, only five cases of associated Gaucher's disease and chronic lymphocytic leukemia (CLL) have been reported in the world literature. The exact relationship of the two diseases to one another has been puzzling, and Gaucher's disease has been viewed as both a cause of and an epiphenomenon to chronic lymphocytic leukemia. In this case, because of the temporal relationship of the two conditions and the confirmation of Gaucher's disease by both histochemical means and electron microscopy, we believe that a cause/effect interaction may exist. However, the exact mechanism by which this may occur is, as yet, speculative.

Bone marrow culture for diagnosis of mycobacterial and fungal infections in febrile patients.

The perception and evaluation of patients with fever are constantly evolving. Due to sophisticated technology and financial constraints, increasing numbers of tests are performed earlier in patient evaluation. One is bone marrow culture for mycobacteria and fungi. To assess the yield of this procedure, we reviewed the results of cultures performed from 1982-1986 at Shands Hospital at the University of Florida. There were 124 patients so evaluated. No fungal cultures were positive. Four mycobacterial cultures were positive: three Mycobacterium avium-intracellulare, all in patients with AIDS (Acquired Immune Deficiency Syndrome), and one Mycobacterium tuberculosis in a patient with disseminated disease. Three patients ultimately found by other means to have disseminated mycobacterial infection were culture negative. We conclude that this procedure is of very low yield and only warranted in the patient with severe immunocompromise or the patient with strong clinical evidence of disseminated tuberculosis.

Selective protection of specific DNA sequences in the heterochromatin of C-banded human Y chromosomes.

The molecular basis of C-banding was investigated by in situ hybridization of human Y chromosome-derived repeated sequences, DYZ1 and DYZ2, to untreated or to alkaline-treated metaphases. Autoradiography of G-banded metaphases showed that both probes hybridized to the long arm of Y. Alkaline hydrolysis significantly reduced grain number for DYZ2 (58%-82%; P less than .05) but not for DYZ1 (P greater than .05). Similar results were observed for interphase nuclei. These findings demonstrated that the heterochromatin of the long arm contains at least two repetitive DNA fractions having two different sensitivities to alkaline hydrolysis. These observations support the notion that DYZ2 maps terminally on the Yq arm and may be nonheterochromatic.

Cancer of the male breast with prolonged survival.

A retrospective review of patients suffering from male breast cancer was carried out at the Shands Teaching Hospital of the University of Florida. Thirteen evaluable cases were analyzed. Three patients were in Stage I, two patients in Stage II, none in Stage III, and eight in Stage IV. Two of the patients with Stage IV disease have had remarkably prolonged survivals of 194 months and 128 months. Such prolonged survivals are unusual. It is possible that the biology of male breast cancer is different from the female, and the disease should be approached more optimistically than it has in the past.