Autopneumonectomy with compensatory lung growth.

A 23-year-old female immigrant from Ethiopia presented with a history of hemoptysis and an abnormal chest x-ray. A computed tomography scan showed that her left lung was greatly shrunken and her right lung was very large but structurally normal. She had a history of multiple respiratory infections as a young child but had been well since the age of five years. Her lung function was within normal limits except for an increased residual volume. It is very likely that her left lung was destroyed early in childhood and that her right lung underwent compensatory growth. She did not show airways obstruction, which is usually seen when compensatory lung growth occurs after surgical removal of lung tissue; this may indicate that, in those cases, the surgery compromised airway function.

Absence of constitutively activating mutations in the GHRH receptor in GH-producing pituitary tumors.

The molecular events leading to the development of GH-producing pituitary tumors remain largely unknown. We hypothesized that activating mutations of the GHRH receptor might occur in a subset of GH-producing pituitary tumors. Genomic DNA samples from 54 GH-producing pituitary tumor tissues were screened for mutations of the GHRH receptor. Eleven homozygous or heterozygous nucleotide substitutions [169G > A (A57T), 338C > T (P113L), 363G > T (E121D), 409C > T (H137Y), 547G > A (D183N), 673G > A (V225I), 749G > A (W250X), 760G > A (V254M), 785G > A (S262N), 880G > A (G294R), 1268G > A (C423Y)] were found in 12 patients (22.2%). The 169G > A substitution (A57T) appears to be a polymorphism (4 patients, 7.4%). E121D and V225I were each found in 2 patients. In 1 patient with the V225I sequence, the substitution was not found in genomic DNA from peripheral leukocytes, suggesting a somatic mutation. A patient with a heterozygous W250X mutation was homozygous for the C423Y substitution. These variant GHRH receptors were studied in transfected TSA-201 cells to evaluate the functional consequences of the amino acid changes. None of the GHRH receptor variants was associated with basal elevation of intracellular cAMP. GHRH induced variable cAMP responses. With the W250X and G294R variants, there was no cAMP stimulation by GHRH, indicating that the mutations are inactivating. Expression of the W250X GHRH receptor on the cell membrane was severely decreased and GHRH binding to the G294R GHRH receptor was impaired. Although GHRH receptor variants are common in GH- producing pituitary adenomas, constitutively activating mutations, as a mechanism for GH-producing pituitary tumors appear to be rare.

Perspective in pituitary adenomas: an end of the century review of tumorigenesis, diagnosis, and treatment.

Significant advances have been made in the molecular biological understanding of pituitary tumorigenesis. These advances will have an impact on the gene therapy of pituitary tumors in the coming century. Transsphenoidal surgery remains the mainstay of treatment for the majority of pituitary adenomas, with endoscopic surgery being used at some centers in select patients. Pharmacotherapy of pituitary adenomas has made great strides in the management of prolactinomas and GH-secreting pituitary adenomas. Finally, radiosurgery has become a very important adjuvant therapy in the treatment of hypersecreting pituitary adenomas.

The history of neurological surgery at Northwestern University.

The residency program in neurological surgery at Northwestern University was founded in 1924 by Loyal Davis and was formally accredited by the American Board of Neurological Surgery in 1946. Allen Kanavel, mentor to Davis, was one of the original members of the Society of Neurological Surgeons. Five individuals have served as chief of neurosurgery at Northwestern: Davis, Paul Bucy, Anthony Raimondi, Albert Butler, and H. Hunt Batjer. Davis was the first surgeon west of the Appalachians to limit his work to neurosurgery. Between 1954 and 1963, there were two independent neurosurgery residency programs at Northwestern, one headed by Davis and the other by Bucy. A master surgeon and superb teacher, Bucy trained more than 65 residents and became one of the greatest authors and leaders in the field of neurosurgery. Neurosurgical training at Northwestern has traditionally emphasized excellence of patient care, strong resident and student teaching, and basic science research. Through the years, a major strength of the program has been its clinical volume and diversity. Four hospitals have played major roles in the program: Northwestern Memorial Hospital (created by the merger of Chicago Wesley Memorial Hospital and Passavant Memorial Hospital), Children's Memorial Hospital, Evanston Hospital, and the Veterans Administration Lakeside Hospital. This article traces the development of neurological surgery at Northwestern, with an emphasis on its historical background and the contributions of Kanavel, Davis, and Bucy. The present philosophy and structure of the training program and the program's future under the direction of Batier are also described.

Complications of transsphenoidal surgery: results of a national survey, review of the literature, and personal experience.

OBJECTIVE: The primary objectives of this report were, first, to determine the number and incidence of complications of transsphenoidal surgery performed by a cross-section of neurosurgeons in the United States and, second, to ascertain the influence of the surgeon's experience with the procedure on the occurrence of these complications. The secondary objective was to review complications of transsphenoidal surgery from the standpoint of their causation, treatment, and prevention. METHODS: Questionnaires regarding 14 specific complications of transsphenoidal surgery were mailed to 3172 neurosurgeons. The data reported were analyzed from the 958 respondents (82%) who reported performing the operation. The neurosurgeons surveyed were asked to estimate the number of transsphenoidal operations performed, to identify any complications observed, and to estimate the percentage of operations that had resulted in any of the 14 specific complications. The 958 respondents were placed into three experience groups, based on the number of transsphenoidal operations performed. The data were analyzed by using chi 2 tests and Spearman correlation coefficients. The secondary objectives were met through a detailed review of the literature, in light of our experience. RESULTS: Of the respondents, 87.3% reported having performed < 200 operations and 9.7% reported 200 to 500 previous operations. The remaining 3% reported more than 500 previous operations. More extensive previous experience with transsphenoidal surgery was associated with a greater likelihood of having witnessed each specific complication. The mean operative mortality rate for all three groups was 0.9%. Anterior pituitary insufficiency (19.4%) and diabetes insipidus (17.8%) were complications with the highest incidence of occurrence. The overall incidence of cerebrospinal fluid fistulas was 3.9%. Other significant complications, such as carotid artery injuries, hypothalamic injuries, loss of vision, and meningitis, occurred with incidence rates between 1 and 2%. An inverse relationship was found between the experience group and the likelihood of complications, as indicated by significant negative Spearman correlation coefficients for all but 2 of the 14 complications listed in the survey (P < 0.05). Thus, increased experience with transsphenoidal surgery seems to be associated with a decreased percentage of operations resulting in complications. Some caution should be exercised in interpreting these data, because they are based on the respondents' estimates. CONCLUSION: Transsphenoidal surgery seems to be a reasonably safe procedure, with a mortality rate of less than 1%. However, a significant number of complications do occur. The incidence of these complications seems to be higher, with statistical significance, in the hands of less experienced surgeons. The learning curve seems to be relatively shallow, because a statistically significantly decreased incidence of morbidity and death could be documented after 200 and even 500 transsphenoidal operations. Better understanding of the indications for transsphenoidal surgery and improved familiarity with the regional anatomy should further lower the incidence of death and morbidity resulting from this procedure in the hands of all neurosurgeons.

Diaphragma sellae meningiomas.

Despite their unique clinical, radiological, and surgical considerations, diaphragma sellae meningiomas remain largely undistinguished from tuberculum sellae meningiomas. On the basis of our experience with 12 patients with diaphragma sellae meningiomas and our review of the literature, we classify these tumors into three groups: Type A, originating from the upper leaf of the diaphragma sellae anterior to the pituitary stalk; Type B, originating from the upper leaf of the diaphragma sellae posterior to the pituitary stalk; and Type C, originating from the inferior leaf of the diaphragma sellae. Each type has specific clinical symptoms. Type A mainly presents with unilateral visual disturbances and visual field defects resembling those of tuberculum sellae meningiomas, although preoperative diabetes insipidus occurred in patients with large tumors. Type B causes fewer visual disturbances, but memory disturbance and hypopituitarism occur. Type C closely resembles nonfunctioning pituitary adenomas; bitemporal hemianopsia and hypopituitarism are common. Multiplanar magnetic resonance images can accurately diagnose the tumor and establish its type. Surgical approaches include the cranio-orbital approach for Types A and B and the transcranial-transsphenoidal approach for Type C. Surgery is more difficult than for tuberculum sellae meningiomas because of the deep location and the difficulty of dissecting Types A and B from the pituitary stalk. Repair of the sphenoid sinus to prevent cerebrospinal fluid leakage is mandatory for Type C tumors.

Tentorial and posterior cranial fossa meningiomas: operative results and long-term follow-up: experience with twenty-six cases.

In spite of significant recent advancements in imaging technology, monitoring [12] and surgical techniques [1,5,7,18,21,24], complete and safe removal of tentorial and posterior fossa meningiomas remains a formidable challenge for most neurosurgeons [6,8,9,14,15,17]. This paper reviews our experience with 28 patients with tentorial and posterior fossa meningiomas.

Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas.

Malignant gliomas have been difficult to treat with chemotherapy. The most effective agent, BCNU (carmustine), has considerable systemic toxicity and a short half-life in serum. To obviate these problems, a method has been developed for the local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers. Implantation of the drug-impregnated polymer at the tumor site allows prolonged local exposure with minimal systemic exposure. In this Phase I-II study, 21 patients with recurrent malignant glioma were treated with BCNU released interstitially by means of a polyanhydride biodegradable polymer implant. Up to eight polymer wafers were placed in the resection cavity intraoperatively, upon completion of tumor debulking. The polymer releases the therapeutic drug for approximately 3 weeks. Three increasing concentrations of BCNU were studied; the treatment was well tolerated at all three levels. There were no adverse reactions to the BCNU wafer treatment itself. The average survival period after reoperation was 65 weeks for the first dose group, 64 weeks for the second dose group, and 32 weeks for the highest dose group. The overall mean survival time was 48 weeks from reoperation and 94 weeks from the original operation. The overall median survival times were 46 weeks postimplant and 87 weeks from initial surgery. Eighteen (86%) of 21 patients lived more than 1 year from the time of their initial diagnosis and eight (38%) of 21 patients lived more than 1 year after intracranial implantation of the polymer. Frequent hematology, blood chemistry, and urinalysis tests did not reveal any systemic effect from this interstitial chemotherapy. Since the therapy is well tolerated and safe, a placebo-controlled clinical trial has been started. The trial will measure the effect of the second treatment dose on survival of patients with recurrent malignant glioma.

Laser-assisted nerve repair in primates.

Studies on the peripheral nerves in rats and other species have helped in the development of laser-assisted nerve anastomosis (LANA), but offer little in evaluating the efficacy of this technique in primates. The authors present a study of LANA in the peripheral nerves of rhesus monkeys. Twelve adult rhesus monkeys underwent bilateral resection of a portion of the peroneal nerve followed by placement of autogenous sural nerve interposition fascicular grafts. The grafts were completed with conventional microsurgical suture technique on one side and with LANA on the other. At 5, 8, 10, and 12 months, the grafted nerves were evaluated for continuity, nerve conduction, and histology (both light and electron microscopy). No significant difference in continuity, conduction velocity, nerve degeneration, nerve regeneration, axon fiber number, or axon fiber density was found in any animal between grafts performed by conventional microsuture and LANA grafts. There was no difference in distal or proximal myelinated fiber density between the LANA grafts and the conventional microsuture grafts. It was concluded that LANA is as effective as microsurgical suture nerve anastomosis in a primate model of nerve repair and grafting.

Reoperation for malignant astrocytoma.

We evaluated 15 consecutive patients with malignant astrocytomas who were reoperated for functional status and survival. Their Karnovsky Performance Status (KPS) was not changed by surgery. None suffered perioperative death, wound infection, or complications. Patients with glioblastoma maintained KPS unchanged for a mean of 13 weeks (median, 10 weeks); with anaplastic astrocytoma, mean, 37.2 weeks (median, 24 weeks). Life spans were approximately twice that of non-reoperated historical controls. Reoperation for patients with recurrent malignant astrocytoma should be seriously considered when a gross total re-resection can be the goal in a patient whose tumor is in an accessible brain region.