Aggressive resection of metastatic disease in selected patients with malignant gastrinoma.

Fifteen patients with Zollinger-Ellison syndrome followed at the National Institutes of Health with extensive metastatic disease had an actuarial 5-year survival of 20%. Therefore, in 1982 a prospective study to examine the effect and feasibility of removing all gross tumor in selected patients with extensive metastatic disease was instituted. Five patients with extensive metastatic gastrinoma confined to the abdomen in whom imaging studies suggested the possibility of complete surgical resection were entered into this study and underwent attempted complete surgical resection and chemotherapy with streptozotocin, doxorubicin, and 5-fluorouracil. Median follow-up was 24 months. Surgical resection of all gastrinoma was possible in 4/5 patients attempted. In one patient in whom all gross disease could not be resected, the residual tumor progressed and the patient died 19 months after operation. All four patients with all disease resected appeared to benefit since all of them had a significant reduction in antisecretory medications and are enjoying normal activity and work. Three patients have had no detectable tumor on follow-up, and two of these patients are clinically and biochemically "cured" with normal fasting gastrin levels and negative provocative gastrin tests at 14 and 32 months. Therefore, aggressive resection of metastatic disease in selected patients with malignant gastrinoma is recommended.     

Dilemma of black community hospitals

This feature of Urban Health covers a wide range of topics related to metropolitan hospitals, both public and private. This month's column discusses a hospital setting with which relatively few practicing physicians are well acquainted--the Black community hospital. More than 500 such hospitals were established in years following the Civil War, but their numbers have dwindled steadily in recent decades to the point where today only a handful survive. A recasting of missions and a thrust into the middle class population are among strategies needed to halt the demise of these institutions, says the author.     

Home parenteral nutrition: a hospital-based program with commercial logistic support

Since home parenteral nutrition was introduced in the 1970's, a number of medical centers have formed successful home parenteral nutrition programs which have reduced expenses to the patient and third party payers by 50 to 73% over in hospital costs. However, the cost of maintaining these programs for training and follow-up has largely been absorbed by the hospital as a nonreimbursable teaching expense. To offset the costs of our growing program in these times of budget "caps," we have established an agreement between our hospital and commercial home care company which provides for patient instruction and follow-up by the hospital parenteral and enteral nutrition team and logistic support by the home care company. We used the average cost of our first five patients to establish a fee schedule which the commercial company agreed to pay the hospital parenteral and enteral nutrition team for its services. This agreement reduces the number of nurses and pharmacists that the commercial company would otherwise have to hire for teaching and follow-up of home care patients, and supports the concept of regional care in medical centers where parenteral and enteral nutrition teams maintain quality control, continuity of care, and efficient teaching programs for patients requiring home parenteral nutrition.     

Anti-Interleukin-6 Therapy Decreases Hip Synovitis and Bone Resorption and Increases Bone Formation Following Ischemic Osteonecrosis of the Femoral Head

Legg-Calvé-Perthes disease (LCPD) is a juvenile form of ischemic femoral head osteonecrosis, which produces chronic hip synovitis, permanent femoral head deformity, and premature osteoarthritis. Currently, there is no medical therapy for LCPD. Interleukin-6 (IL-6) is significantly elevated in the synovial fluid of patients with LCPD. We hypothesize that IL-6 elevation promotes chronic hip synovitis and impairs bone healing after ischemic osteonecrosis. We set out to test if anti-IL-6 therapy using tocilizumab can decrease hip synovitis and improve bone healing in the piglet model of LCPD. Fourteen piglets were surgically induced with ischemic osteonecrosis and assigned to two groups: the no treatment group (n = 7) and the tocilizumab group (15 to 20 mg/kg, biweekly intravenous injection, n = 7). All animals were euthanized 8 weeks after the induction of osteonecrosis. Hip synovium and femoral heads were assessed for hip synovitis and bone healing using histology, micro-CT, and histomorphometry. The mean hip synovitis score and the number of synovial macrophages and vessels were significantly lower in the tocilizumab group compared with the no treatment group (p < .0001, p = .01, and p < .01, respectively). Micro-CT analysis of the femoral heads showed a significantly higher bone volume in the tocilizumab group compared with the no treatment group (p = .02). The histologic assessment revealed a significantly lower number of osteoclasts per bone surface (p < .001) in the tocilizumab group compared with the no treatment group. Moreover, fluorochrome labeling showed a significantly higher percent of mineralizing bone surface (p < .01), bone formation rate per bone surface (p < .01), and mineral apposition rate (p = .04) in the tocilizumab group. Taken together, tocilizumab therapy decreased hip synovitis and osteoclastic bone resorption and increased new bone formation after ischemic osteonecrosis. This study provides preclinical evidence that tocilizumab decreases synovitis and improves bone healing in a large animal model of LCPD. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Clinical and pathological analysis of spinal cord astrocytomas in children

Twelve children with pathologically confirmed, well-differentiated spinal cord astrocytomas were studied, and correlations among the degree of resection, pathological characteristics, and time of recurrence were examined. Eight tumors were sampled for biopsy or subtotally resected, and 4 were thought to have been totally removed. Clinical recurrence was seen in 4 of 12 patients, 2 of whom died of their disease. The time to recurrence was 1, 2, 2, and 35 years, respectively. The other 8 children remain free of symptoms, with follow-up ranging from 6 months to 35 years (mean, 8.8 years). In 3 of 8 patients who underwent biopsy or subtotal resection, the tumor recurred, and 2 patients died, whereas there was one recurrence in the patients in whom a "total" resection had been obtained. The histologically well-differentiated nature of the lesions correlated well with the relatively prolonged clinical course seen in this series during the period of observation. The relatively long clinical courses seen in our limited series should be considered before high-risk therapy for spinal cord astrocytomas in children is implemented. The presence of four pilocytic astrocytomas in this group was of special interest, and it seems likely that these discrete neoplasms can be distinguished from the more infiltrating fibrillary astrocytic neoplasms by magnetic resonance imaging with enhancement with gadopentetate dimeglumine.     

Effects of haloperidol or SCH-23390 on ethanol-induced conditioned taste aversion.

Dopaminergic systems are thought to play an important role in the motivational effects of ethanol. The present experiments examined the effects of haloperidol (a D2 antagonist) and SCH-23390 (a D1 antagonist) on the acquisition of ethanol-induced conditioned taste aversion. In four separate experiments, adult male Swiss-Webster mice were acclimated to a 2-h/day water restriction regimen. Subsequently they received four conditioning trials consisting of 1-h access to either 0.2 M NaCl (experiments 1-3) or 0.15 % w/v saccharin (experiment 4). After flavor access on trials 1-3, subjects received either haloperidol (0.1, 0.15, or 0.3 mg/kg), SCH-23390 (0.05 mg/kg), or saline followed 30 min later by 0, 2, or 4 g/kg ethanol. Ethanol-flavor pairings reduced subsequent flavor intakes, indicating the development of conditioned taste aversion. Neither haloperidol of SCH-23390 reduced flavor intakes in the absence of ethanol. However, both haloperidol and SCH-23390 reduced ethanol-conditioned aversion depending on ethanol dose and conditioned flavor. These results are consistent with the notion that dopaminergic processes are important for the development of ethanol-induced conditioned taste aversion, and the notion that dopaminergic receptor systems influence both positive and negative motivational effects of ethanol.     

Prenatal ultrasonography and early surgery for congenital cystic disease of the lung.

With the recent advent of prenatal ultrasound as a routine screening procedure, diagnosis of congenital cystic lung disease has been made in utero, raising the possibility of elective surgery for these lesions early in infancy before the patient develops respiratory distress or potentially life-threatening infection. From 1979 to 1989 six cases of congenital lung cyst were diagnosed in utero by prenatal ultrasound and followed during pregnancy. Two of the six were not confirmed after birth because the mothers preferred an abortion. The remaining four cases were studied periodically during gestation by ultrasonography. At birth, the first infant developed respiratory distress and underwent urgent left upper lobectomy and left lower segmentectomy at age 18 hours. The other three underwent elective lobectomy at age 10 days, 3 months, and 7 months, respectively. The fourth infant had a normal chest x-ray and ultrasound at birth, and the congenital cysts were confirmed by computed tomography scan. The pathological diagnosis in all four cases was cystic adenomatoid malformation. In two cases, intraoperative measurement of pulmonary function demonstrated significant improvement after resection of the affected lobe. We conclude that congenital lung cysts can be accurately diagnosed by prenatal ultrasound "screening" as early as 18 to 24 weeks' gestation. Advantages of early diagnosis include the option of moving the mother and unborn child to a high-risk obstetrical center for urgent operation on the newborn infant if necessary. Otherwise, once the diagnosis is confirmed, surgical correction can be performed electively and safely before respiratory distress or pulmonary infection complicates the infant's growth and development.     

Fatal adenovirus pneumonia: Clinical and pathological features.

A review of autopsies of 107 young children with pneumonia showed that 15 children (14%) had adenovirus infections, the diagnosis being based on characteristic histopathological and ultrastructural features in the lungs. Eleven (73%) of the cases of adenovirus infection followed on measles infection, and it is suggested that some became infected with adenovirus after admission to hospital. A review of clinical aspects revealed no unique features. Histopathological examination of tissues showed a common picture of necrotising bronchopneumonia, with minor degrees of rental tubular damage, infiltrates of large mononuclear cells in spleen and nodes, and an absence of lymphoid germinal centres. On light microscopy, "rosette" and "smudge" cells were seen in these cases, and two patterns of virus particle distribution in infected cells were seen ultrastructurally. It is postulated that "smudge" cells contain numerous crystalline viral arrays.