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The middle cranial fossa approach to lesions of the geniculate ganglion and internal auditory canal preserves cochlear function and affords access to the lateral internal auditory canal. The labyrinthine portion of the facial nerve tends to course near the basal turn of the cochlea, just beneath the middle cranial fossa floor, and is usually dissected in this approach. To determine the distance from the labyrinthine portion of the facial nerve to the basal turn of the cochlea, measurements were obtained in the temporal bones of 24 subjects (48 ears) 9 to 76 years of age. These subjects had no history of facial nerve or ear disease, and had normal audiograms. The distances ranged from 0.06 to 0.80 mm, with 21 of 24 right ears (87.5%) showing distances less than the standard size of the smallest diamond drills (0.6 mm), and 18 of 24 (75%) less than 0.5 mm. Incidental note is made of the distance from the geniculate ganglion to the ampulla of the superior semicircular canal, which ranged from 2.06 to 4.88 mm in the 48 specimens. These measurements can serve as guidelines for the surgeon working in the middle cranial fossa.

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Obstruction of the cochlear scale by ossification and fibrosis, which can now be imaged by computed tomography, has been proposed as a predictor of ganglion cell survival. Subjects for this histopathologic temporal bone study were 12 profoundly deaf patients with labyrinthitis ossificans. Controls without ossification were 16 normal-hearing patients and 16 profoundly deaf patients. All temporal bones were graphically reconstructed. Computerized image analysis obtained the percentage of scalar obstruction in 12 temporal bones with labyrinthitis ossificans. Statistical analyses could demonstrate no relationship between spiral ganglion cell survival and obstruction. There was much interindividual variability in ganglion cell count among the 44 temporal bones. Ganglion cell survival was significantly less in the two deafness groups than in the normal group, but did not differ significantly between the two deafness groups. Therefore, cochlear labryinthitis ossificans is not a preditor of ganglion cell survival and should not be a contraindication to cochlear implantation.

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In an Illinois Cancer Center phase II trial, fludarabine phosphate was administered to a total of 14 patients (9 men, 5 women) with advanced, measurable, gastric adenocarcinoma. Fludarabine phosphate was given as a rapid intravenous (IV) bolus at a starting dose of 20 mg/m2/d for the first 5 days of a 28-day cycle. For subsequent cycles, the dose was escalated in increments of 2 mg/m2/d, provided that no toxicities greater than grade 1 were noted. In cases of grade 3 toxicity, dose reductions of 2 mg/m2/d were required, and patients who experienced grade 4 toxicities were removed from study. Receiving one complete 5-day course of fludarabine phosphate and surviving for 4 weeks on study were required for a patient to be evaluable for response. None of the patients responded to treatment. Although fludarabine phosphate was ineffective against gastric adenocarcinoma in this study, toxicity was acceptable at the 20 mg/m2/d times 5 every 28 days dose and schedule.

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Twelve patients with recurrent, metastatic, or inoperable gastric adenocarcinoma were enrolled in an Illinois Cancer Center phase II trial of amonafide (nafidimide), a novel compound that acts as a DNA intercalator. Treatment consisted of a 60-minute infusion of amonafide which was administered daily for 5 consecutive days every 3 weeks at a starting dose of 300 mg/m2/d. Doses were modified according to the grade of toxicity experienced and eight patients underwent dose escalations. All 12 patients were evaluable for response and toxicities were predominantly hematologic. Stabilization of disease for at least 28 days was observed in seven patients and disease progression was noted in five. The median survival was 7.4 months. Doses were sufficient to produce severe bone marrow toxicity in one-third of the patients treated. None of the patients responded to therapy, implying a true response rate less than .221. Based on the results of this study, amonafide showed no activity against gastric adenocarcinoma; however toxicity appeared acceptable at the 300 mg/m2/d x 5 consecutive days every 3 weeks dose and schedule.

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Sixteen patients with metastatic melanoma entered this phase II study of the efficacy of monthly cycles of Bisantrene. Toxicity was characterized by leukopenia, resulting in the hospitalization of one patient for a febrile incident, and superficial phlebitis. The results were similar to those of previous studies, in that among the 13 patients evaluable for response (six previously untreated with chemotherapy) there were no responses.

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A phase II trial of 4' Deoxydoxorubicin (DXDX) was conducted in unresectable previously untreated non-small cell lung cancer patients. DXDX was administered every 3 weeks by short intravenous infusion at a starting dose of 30 mg/m2, with dose escalation to 40 mg/m2 toxicity permitting. Four responses, all partial, were observed in 35 evaluable patients, for a response rate of 11% (95% confidence limits 3.2% and 26.7%). Myelosuppression was the dose-limiting toxicity. Cardiotoxicity was not seen. DXDX has minimal activity against non-small cell lung cancer as a single agent at the dosage used in this study.

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A phase II trial of spirogermanium was conducted in advanced previously untreated non-small cell lung cancer patients. The drug was given by intravenous infusion 3 times per week for 2 weeks, twice per week for the next 2 weeks, and then weekly. Starting dose was 125 mg/m2, and dose escalation of 25 mg/m2 per week was required in the absence of toxicity to a maximum dose of 200 mg/m2 per infusion. Fifteen eligible patients were treated, and no objective responses were seen. Primary toxicity was neurologic and reversible after withdrawal of the drug. We conclude that spirogermanium is not active against non-small cell lung cancer in the dosage used in this study.

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Fludarabine Phosphate (FP), the 2-fluoro, 5'phosphate derivative of adenosine arabinoside (ara-A), was studied in 18 patients with advanced renal cell carcinoma. These patients had measurable disease and had not received chemotherapy. FP was administered at a loading dose of 20 mg/m2 followed by a 48-hour infusion at 30 mg/m2/day given every 21 days. There were no complete or partial responses seen. Toxicity was mainly hematologic, with leukopenia most commonly observed. FP given in this manner had no activity in advanced renal cell carcinoma.

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The recently developed enzyme immunoassay for estrogen receptors is more simple to perform with quality assurance than conventional steroid-binding assays with radioactive labeled estrogen. However, it is not known how well the results of the two assays agree for normal human uterine samples. We compared enzyme immunoassay (Abbott estrogen receptor enzyme immunoassay) and steroid-binding assay of normal human endometrium and myometrium. Low-salt, "cytosol" estrogen receptor determinations were performed by dextran-coated charcoal assay, and high-salt, "nuclear" estrogen receptors were measured by controlled pore glass bead assay. Results showed excellent correlation (p less than 0.0001) for cytosol estrogen receptor of endometrium (r = 0.95) and myometrium (r = 0.79) and also for a smaller number of nuclear estrogen receptors of myometrium (p less than 0.01, r = 0.69). Good agreement between steroid-binding assay and enzyme immunoassay was seen for estrogen receptors of both proliferative and secretory phase samples. Thus the data indicate that the simpler estrogen receptor enzyme immunoassay is useful to measure estrogen receptor in the normal uterus. Furthermore, with this sandwich assay, there is no evidence for the existence of significant quantities of receptor fragments that do not bind estrogen.

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We analyzed 96 patients who had surgery with T1N0M0 or T2N0M0 nonsmall cell lung cancer (NSCLC) to identify survival rates and recurrence patterns in well-staged patients and to evaluate adjuvant therapy. Preoperative staging included chest x-ray, gallium 67 scanning, and bronchoscopy in all patients. At thoracotomy, multiple mediastinal lymph node sites were routinely sampled. The results included an operative mortality rate of 5.2%, and the actuarial 5-year survival rate of all patients was 70.0%. Survival of T1N0 (n = 44) and T2N0 (n = 47) patients was 72.1% and 68.3%, respectively (p = NS). Survival was not affected by type of surgery, cell type, sex, age, or race. Late death was due to recurrence in 12 patients, a new airway malignancy in three, and a noncancer problem in six. Disease recurred in 15 patients: four (9.1%) T1N0 patients versus 11 (23.4%) T2N0 patients, p less than 0.05. Recurrence was local in four patients and distant in 11. Second lung cancers developed in six patients at a mean interval of 65.7 months after resection. A prospective, randomized trial of systemic immunotherapy with bacillus Calmette-Guerin (BCG) skin scarification was carried out in 29 patients. Survival in those patients receiving BCG was 85.9% compared with 63.9% for control subjects (p = 0.075) and 69.6% for patients not in the study (p = 0.077). The following conclusions can be made: Resection for well-staged, modified stage I NSCLC results in a 5-year survival rate of 70%. Nearly half the deaths are unrelated to recurrence of the original cancer. Recurrences are more frequent in T2N0 patients, but there is no survival difference compared with T1N0 patients. Systemic recurrences are more frequent than local recurrences, and there is an appreciable incidence of second lung cancers. Adjuvant chemotherapy or radiation therapy does not seem justified, but systemic immunotherapy holds sufficient promise to warrant further investigation.

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Breast cancers of postmenopausal patients at high risk for recurrence participating in an adjuvant therapy protocol were independently assayed for estrogen receptor by conventional dextran-coated charcoal steroid binding assays and by immunocytochemistry (ER-ICA) to compare the two assays and to assess the prognostic usefulness of ER-ICA. The ER-ICA was based on a monoclonal antibody to the estrogen receptor and was applied to lightly fixed, frozen sections of the cancers. Excellent agreement was found between the two estrogen receptor methods. It was found that a combination of the distribution of ER-ICA stained cells and the overall staining intensity gave a statistically significant correlation with the quantitative estrogen receptor dextran-coated charcoal steroid binding assay value. In addition, the overall appraisal of the lesion as ER-ICA positive or negative as well as the ER-ICA staining intensity and proportion of ER-ICA stained cancer cells related to patient disease-free interval and survival, independent of patient lymph node involvement. This relationship of ER-ICA status to prognosis appeared not to relate only to responses to adjuvant tamoxifen treatment since it also was observed with patients who did not receive the antiestrogen.

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Forty-one patients with two subtypes of stage IIIM0 non-small-cell lung cancer treated over a 7-year period were evaluated. The first group of 20 patients had ipsilateral parietal pleural involvement not contiguous with the primary tumor but no distant metastases. Fifteen had positive pleural fluid cytology, seven with positive pleural biopsy in addition; four had extensive pleural studding or a positive biopsy but no effusion; and one had negative pleural fluid cytology. Treatment consisted of radiation therapy followed by combination chemotherapy in all. Due to symptoms, eight patients first had fluid drainage with or without sclerosis and two patients had a pleurectomy. Nine had progressive pleural disease despite the local treatment. To all modalities of therapy, only two patients had a partial response. One patient who had a pleurectomy lived 25 months. Median survival was 6.9 months. Cause of failure involved local progression in 17 patients. There was no difference in median survival by age, sex, histology, side of effusion, location of nodal disease, or use of local therapy. The second group of 21 patients had localized involvement of the parietal pleura by the primary tumor. There was deeper chest wall invasion in nine. All patients were rendered free of known disease by surgical resection, were stage T3N0-2M0, and received radiation and chemotherapy in addition to resection. The median survival was 13.5 months. There was local recurrence in nine patients but only one developed an effusion. Five patients were alive at 29-82 months. No variable unfavorably influenced survival except a central versus peripheral primary. Thus, the median survival of the patients in the first group with multiple sites of pleural involvement was similar to that of patients with distant metastases but with the cause of failure primarily local progression. In the majority of patients in the second group, parietal pleural and chest wall involvement, even with nodal metastases, did not translate into local failure, and long-term survival was possible.

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Clinical, histologic, and cytogenetic features in 63 patients with a therapy-related myelodysplastic syndrome (t-MDS) or acute nonlymphocytic leukemia (t-ANLL) following cytotoxic chemotherapy or radiotherapy for a previous disease were analyzed. Eleven patients had received only radiotherapy for the primary disorder. In most cases, high doses had been administered to treatment ports that included the pelvic or spinal bone marrow. Twenty-one patients had received only chemotherapy for their primary disease, all for more than 1 year and all but one with an alkylating agent, either alone or in combination with other drugs. Thirty-one patients had received both radiotherapy and chemotherapy, either concurrently or sequentially. A clonal chromosomal abnormality was observed in marrow or blood cells from 61 of the 63 patients (97%). Fifty-five patients (87%) had a clonal abnormality of chromosomes no. 5 and/or 7 consisting of loss of all or part of the long arm of the chromosome. The critical chromosome region that was consistently deleted in all 17 patients with del(5q) comprised bands q23 to q32. In addition to nos. 5 and 7, five other chromosomes (no. 1, 4, 12, 14, and 18) were found to be nonrandomly involved. Both t-MDS and t-ANLL are late complications of cytotoxic therapies that have distinctive clinical and histologic features and are associated with characteristic aberrations of chromosomes no. 5 and 7. It seems likely that these two chromosomes contain genes involved in the pathogenesis of these hematopoietic neoplasms.

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Twenty-two patients with advanced-stage, non-small cell bronchogenic carcinoma were treated in a pilot study with a combination of vindesine, etoposide, and cisplatin (VEDDP). All patients had been previously treated with a non-cisplatin-containing regimen and had documentation of progressive disease. Median duration of VEDDP therapy was 2.6 months. Only one patient had a minor response. Median survival from start of protocol therapy was 3.7 months; the overall survival from start of primary therapy was 13.5 months. The only significant variable possibly affecting survival was achieving a minor response or stable disease (5.0 months for minor response/stable disease from start of VEDDP vs 3.2 months for progressive disease, P = 0.016). Hematologic toxicity was moderate to severe in 14 patients and prevented completion of two full cycles in seven patients. We conclude that VEDDP is ineffective in inducing a response in patients with refractory, advanced-stage non-small cell bronchogenic carcinoma in the dose and kinetic schema used in this pilot study.

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In order to determine whether combination chemotherapy offered any advantage over single-agent therapy in cases of metastatic non-small cell bronchogenic carcinoma, we performed a randomized study in 56 patients comparing combination chemotherapy (cyclophosphamide, doxorubicin, methotrexate, procarbazine, leucovorin--CAMP-L) with a regimen in which the same drugs were given sequentially (methotrexate/leucovorin followed by cyclophosphamide/doxorubicin at progression). Of the patients receiving the combination, 52% (14 of 27) had either a partial response or stable disease, compared to 17% (5 of 29) in the sequential group. Of the patients with adenocarcinoma, those in the combination group had a significantly longer survival than those treated in the sequential group (medians, 10.0 vs 2.8 months; P less than 0.01); such a difference could not be demonstrated for patients with squamous carcinoma. Patients who achieved a partial response had a median survival of 15.3 months; those with stable disease survived a median of 10.0 months; and those with no response survived a median of 2.5 months (P less than 0.0001). Four patients died from chemotherapy-related complications: three from methotrexate toxicity and resultant infection and one from pneumonia associated with neutropenia. We conclude that the short survival of non-responding patients and the survival benefit accompanying response or stabilization make early aggressive combination therapy useful for patients with metastatic non-small cell lung cancer.

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This study defines the components of distal esophageal sphincter function which predict gastroesophageal competence and examines the mechanisms by which three antireflux procedures restore competence to the cardia. In a prospective study, the reflux status of 391 patients was determined by 24 hour pH monitoring. Distal esophageal sphincter pressure and length of sphincter exposed to the positive pressure environment of the abdomen was measured by esophageal infusion manometry. Similar pre- and postoperative studies were performed in 45 patients who were randomized to three equal groups for the Hill, Belsey and Nissen antireflux procedures. Two hundred sixty-seven (68 percent) of the 391 patients had a positive 24 hour pH test. Competence of the cardia was related to pressure in the distal esophageal sphincter, to the length of sphincter in the abdomen and to an interaction between both (all p less than 0.05). Thus, competence of the cardia requires an adequate pressure and length of sphincter in the abdomen. In determining competence, the pressure and length effects are not additive, but have an interacting relationship. Sphincter pressure and abdominal length are independently corrected by surgery. Restoration of competence requires increases in both. The gastric fundic wrap best augments distal esophageal sphincter pressure by application of normal functioning smooth muscle to the lower esophagus. Sphincter dynamics are normal after a wrap as the gastric fundus and distal esophageal sphincter share the functions of synchronous contractions and simultaneous relaxation on deglutition.

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Reproductive histories were compared for 226 DES-exposed and 203 -unexposed daughters whose mothers participated in a double-blind evaluation 27 years before. Irregular menstruation was slightly more common among the exposed (10%) than among the unexposed (4%). Nineteen of the exposed and only four of the unexposed had primary infertility. Among those at risk, 86% of the unexposed and 67% of the exposed had become pregnant. The reasons for these differences are not known. Comparison of evaluable first pregnancy outcome revealed full-term live birth to be more common among the unexposed (85%) than the exposed (47%). Premature live birth was experienced by 22% of the exposed but only 7% of the unexposed. Nonviable outcomes of stillbirth, neonatal death, miscarriage and ectopic pregnancy occurred in 31% of the exposed and 8% of the unexposed. The difference in pregnancy outcomes between the groups is highly significant. The DES-exposed with transverse cervicovaginal ridges were more likely to experience a nonviable outcome. Overall 82% of the exposed and 93% of the unexposed had at least one live offspring.

PIP: Reproductive histories were compared for 226 diethylstilbestrol (DES) exposed and 203 unexposed daughters whose mothers participated in a double-blind evaluation 27 years earlier. Complete prenatal medication records were available for 389 DES exposed and 395 unexposed daughters from the original study. Interviews were conducted from January 1978 to August 1979 at the time of follow-up gynecologic visits or by telephone or mail for those unable to come for an examination. Irregular menstruation was slightly more common among the exposed (10%) than among the unexposed (4%). 19 of the exposed and 4 of the unexposed had primary infertility. Among those at risk, 86% of the unexposed and 67% of the exposed had become pregnant; the reasons for these differences are unknown. Comparison of evaluable 1st pregnancy outcome revealed full-term live birth to be more common among the unexposed (85%) than the exposed (47%). Premature live birth was experienced by 22% of the exposed and 7% of the unexposed. Non-viable outcomes of stillbirth, neonatal death, miscarriage and ectopic pregnancy occurred in 31% of the exposed and 8% of the unexposed. The difference in pregnancy outcomes between the exposed and the unexposed groups is highly significant. The DES-exposed with transverse cervicovaginal ridges were more likely to experience a non-viable outcome. 82% of the exposed and 93% of the unexposed had at least 1 live offspring.

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