P53 overexpression as an indicator of overall survival and response to treatment in osteosarcomas

The p53 gene located at chromosome 17pl3 is found to be altered (allelic loss or other mutation) in multiple human cancers, including osteosarcomas. The mutated gene produces a protein with a prolonged half-life thus rendering it detectable by conventional immunohistochemistry. We examined the correlation between p53 expression and clinical prognosis as well as response to therapy. Twentyone patients with previously untreated and histologically verified highly malignant osteosarcoma were used for this study. Biopsy material taken both prior to the start of COSS 91 protocol and at the time of surgery (ten weeks later) was examined for alterations in p53 protein expression and drug resistance. Two patients who had strong (+++) p53 protein expression and three others who became positive during the chemotherapy had significantly worse prognosis (all of them died within one year) than those who showed no p53 expression both at biopsy and after chemotherapy (all 11 patients are alive, average follow-up time: 3.5 years). All patients who showed any kind of positive p53 protein expression on initial biopsy were non-respon-ders to chemotherapy. In contrast, 69% (9 out of 13) of those who exhibited no p53 expression on initial biopsy were responders or intermediate responders to chemotherapy. We concluded that p53 expression may be a useful prognostic factor in osteosarcomas. The direct correlation between p53 positive expression and resistance to therapy can help in identifying patients who are in need of a more vigorous or different chemotherapeutical protocol.     

Physician choice criteria: factors influencing patient selection of generalists versus specialists

This paper presents the results of an exploratory study designed to (1) ascertain the primary sources of information patients use when selecting physicians and (2) identify differences in patient selection factor importance by type of physician under consideration (specialists versus generalists). The results support previous research which finds word-of-mouth and physician referrals the primary sources of information. Selection factors considered important when selecting a generalist were significantly different from factors considered important when selecting a specialist. Implications of the study's findings for effective physician marketing and future research are discussed.     

"Stockless" cost reduction in the operating room

St. Paul-Ramsey Medical Center in St. Paul, MN became one of the first hospitals in the United States to initiate a "stockless" par level inventory system. Successes with stockless led the hospital to look at implementing it in the OR to achieve a reduction of expense to revenue. Materiel Management and Surgical Services discussed a number of issues relevant to implementing a stockless program, including product flow, accuracy and cost of case carts and preference cards, item pricing, committed usage of items brought into the system and establishment of a steering committee. Specific OR issues and practices required evaluation and adjustment, such as the routine use of emergency direct ordering. Information systems support was brought in and a products committee established to do education and oversee the program. Savings for 1993-94 were $185,146.     

Patterns of success and failure with laparoscopic Toupet fundoplication

Background: Advocates of the Toupet partial fundoplication claim that the procedure has a lower rate of the side effects of dysphagia and gas bloat than a complete Nissen fundoplication. However, there is increasing recognition that reflux control is not always as good with the Toupet procedure as with the Nissen. Therefore, we set out to evaluate the factors contributing to success and failure in patients who underwent laparoscopic modified Toupet fundoplication (LTF). Methods: A total of 143 patients undergoing LTF for documented gastroesophageal reflux disease (GERD) were evaluated prospectively in regard to their outcomes over a 4-year period. All patients had preoperative esophagogastroduodenoscopy (EGD) and manometry; 24-h pH testing was used selectively. Esophageal manometry was requested of all patients 6 weeks postoperatively. Clinical follow-up was by office visit or questionnaire every 6 months after surgery; patients with significant problems were investigated further. Failure was defined as the development of recurrent reflux documented by endoscopy, 24-h pH test, or wrap disruption on barium swallow, or severe dysphagia persisting >3 months and requiring surgical revision. Results: At a mean follow-up of 30 months (range, 3–51), 21 of 143 patients failed LTF; two had dysphagia and 19 had recurrent reflux. Failure was associated with preoperative findings of a defective lower esophageal sphincter (LES) (14/21), complicated esophagitis (13/21), and failure to divide short gastric vessels (12/19) (chi-square p < 0.05). Defective esophageal body peristalsis, present in 14 patients, resulted in failure in six cases. Presence of either complicated esophagitis or a defective LES was associated with a 3-year 50% success rate, whereas presence of mild esophagitis and a normal LES was reflected in a 96% 3-year success rate. Conclusion: Laparoscopic Toupet fundoplication should be reserved for milder cases of GERD, as assessed by manometry and endoscopy. Received: 29 June 1998/Accepted: 2 July 1999     

Influence of the optical axis-to-target view angle on endoscopic task performance

BACKGROUND: The location of the optical port and the choice of endoscope determine the angle subtended between the optical axis of the endoscope and the plane of the operation target: the optical axis-to-target view (OATV) angle. The aim of the study was to investigate the influence OATV angle on endoscopic task performance. METHODS: The Dundee Endoscopic Psychomotor Tester was used for objective assessment of endoscopic task performance. Ten surgeons carried out a standard task with the optical axis of the endoscope subtending 90 degrees, 75 degrees, 60 degrees and 45 degrees to the target surface. Each subject underwent three test sessions. Each session consisted of one run with each of the OATV angles in a random order. The outcome measures were the errors rate, the execution time, and the force applied on the target. RESULTS: The 90 degrees OATV angle had the best accuracy, the shortest execution time, and the lowest force applied on the back plate. The errors rate increased from 17% with the 90 degrees OATV angle to 79% with the 45 degrees angle. There was a significant increase in execution time and force with the decrease in the OATV angle (p < 0.0001). CONCLUSIONS: The best task performance is obtained when the optical axis of the endoscope is perpendicular to the target plane.     

Intracranial extension of inverted papilloma: An unusual and potentially fatal complication

BACKGROUND: The purpose of this article is to define the outcome of intracranial extension of inverted papilloma and outline a rationale for management of this rare clinical presentation. METHODS: A review of patients with intracranial extension of inverted papilloma reported in the literature (18 patients), or treated in our institution (3 patients ) was performed. The data of these 21 patients were consolidated with regard to clinical presentation, treatment, and outcome. Nine patients, including 1 of our cases, had coexisting squamous cell carcinoma and therefore were excluded from the analysis. Twelve patients with "pure" inverted papilloma formed the basis of this study. RESULTS: The majority of patients (83%) with intracranial inverted papilloma had recurrent disease. Patients with extradural disease had a survival rate of 86% with an average follow-up of 4.4 years. Eighty-six percent of these survivors were treated with craniofacial resection. In contrast, 75% of patients with intradural inverted papilloma were dead of disease with an average follow-up of 9.3 months regardless of the treatment modality. CONCLUSIONS: Intracranial extension of inverted papilloma is mostly associated with recurrent disease. Intracranial extradural inverted papilloma can be effectively controlled with craniofacial resection. Intracranial intradural involvement of inverted papilloma has a poor prognosis regardless of treatment. Aggressive treatment of intranasal inverted papilloma may be the most important factor in preventing intracranial presentation.     

Propionibacterium as a cause of postneurosurgical infection in patients with dural allografts: report of three cases

OBJECTIVE AND IMPORTANCE: Although Propionibacterium acnes is a common inhabitant of human skin, it is an uncommon pathogen in postoperative infections. We report three cases of postoperative wound infection/osteomyelitis caused by P. acnes. CLINICAL PRESENTATION: Three patients underwent craniotomy for a supratentorial meningioma and had a dural allograft at the time of closure. The patients presented several weeks after surgery with clinical evidence of a wound infection. INTERVENTION: All patients were diagnosed with P. acnes infection and treated for this pathogen with appropriate antibiotics. The bone flap was removed in two patients. After antibiotic therapy, all patients demonstrated no further evidence of infection. CONCLUSION: To our knowledge, this is the first published report of P. acnes infection in patients with a dural substitute. The source of infection cannot be confidently ascertained; however, two patients had strains of P. acnes from one brand of graft, which were indistinguishable by pulsed field gel electrophoresis typing.     

Chemotherapy,early surgical reassessment,and hyperfractionated abdominal radiotherapy in stage III ovarian cancer: results of a gynecologic oncology group study

PURPOSE: To determine outcomes and treatment toxicities in patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma treated with three courses of cisplatin-cyclophosphamide, surgical reassessment (SRA), and hyperfractionated whole abdominal irradiation (WAI). METHODS AND MATERIALS: Forty-two eligible patients entered this prospective Phase II study conducted by the Gynecologic Oncology Group (GOG). Disease characteristics were as follows: age range, 32-76 years (median 58); Stage IIIA (n = 1, 2%), IIIB (n = 2, 5%), IIIC (n = 39, 93%); histology-serous papillary (n = 21, 50%); other (n = 21, 50%); Grade 1 (n = 1, 2%); 2 (n = 14, 33%); 3 (n = 27, 54%); residual disease after initial surgery (present: n = 23, 55%; absent: n = 19, 45%). Five patients progressed while on chemotherapy, could not be effectively cytoreduced, and were not eligible for WAI. Of the remaining 37 patients, 35 received WAI. Surgical reassessment was not performed in five patients. RESULTS: Of 37 patients with known SRA status after chemotherapy, 21 (57%) were grossly positive, 4 (11%) were microscopically positive, and 12 (32%) were negative. Based on measurements recorded following initial laparotomy and surgical reassessment, progression during chemotherapy was noted in 40%, stage disease in 37%, and objective response in 23%. Toxicity during hyperfractionated WAI was limited and reversible. No patient beginning WAI failed to complete or required a significant treatment break. Following WAI, six patients underwent laparotomies for abdominal symptoms; five had recurrent disease. Five additional patients were managed conservatively for small bowel obstruction (SBO) or malabsorption, of whom three subsequently developed recurrence. Twenty-two patients having pelvic boosts were significantly more likely to require management for gastrointestinal morbidity (p = 0.0021). Considering all eligible patients, median disease-free and overall survivals were 18.5 and 39 months, respectively. Considering patients completing chemotherapy and WAI, median disease-free and overall survivals were 24 and 46 months, respectively. CONCLUSIONS: (a) Disease progression occurred within three cycles of cisplatin and cyclophosphamide chemotherapy in 40% of patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma. (b) Following limited chemotherapy, hyper-fractionated WAI was acutely well tolerated. (c) Late radiation-related toxicity was observed in only three patients (8.6%) in the absence of recurrent disease. Late gastrointestinal morbidity was significantly associated with the administration of a pelvic radiotherapy (RT) boost. (d) Short duration chemotherapy followed by SRA and hyperfractionated WAI without a pelvic boost is a promising management option for patients with optimal Stage III ovarian cancer. A Phase III trial will be necessary to determine how this treatment strategy compares with chemotherapy or RT alone in this patient population.     

Effect of dietary butylated hydroxyanisole on the mouse hepatic monooxygenase system of nuclear and microsomal fractions

The effect of butylated hydroxyanisole (BHA) administrationon the hepatic monooxygenase system of nuclear and microsomalfraction was investigated in male mice. Addition of BHA to thediet significantly lowered the content of cytochrome P-450 inliver nuclei and increased the specific activity of NADPH-cytochromec reductase and the content of cytochrome b₅ in liver microsomes.Incubation of benzo[a]pyrene (BP) with liver nuclei from BHA-fedmice resulted in inhibition of binding of BP metabolites tonuclear macromolecules by 50% compared with control. However,there was no effect of BHA on the binding of BP metabolitesto macromolecules when BP was incubated with added DNA and livermicrosomes from BHA-fed mice. It has been postulated that modificationof nuclear monooxygenases by BHA may play a role in the inhibitoryeffect of BHA on BP carcinogenesis.     

The effect of growth hormone on the growth failure of chronic renal failure

To investigate the effects of growth hormone (GH) on the reversal of growth failure in uremia, recombinant human GH (rhGH) was administered to rats with chronic renal failure (CRF). The dosage of rhGH was 3 IU/day (i.p.) for 13 days after the induction of CRF by 5/6 nephrectomy. Animals were classified into four groups: untreated nephrectomized rats (NX,n=40), GH-treated nephrectomized rats (NX+GH,n=18), sham-operated rats fed ad libitum (SHAMAL,n=27), and sham-operated rats pair-fed with 10 NX rats (SHAMPF,n=10). NX and NX+GH rats developed a similar and moderate degree of CRF, serum urea nitrogen being (mean±SEM) 49±3 and 54±4 mg/dl, respectively, compared with 16±4 and 19±0 mg/dl in SHAMAL and SHAMPF groups. Weight (56.0±3.3 g) and length (3.5±0.1 cm) gains of NX rats were lower than those of SHAMAL rats (94.2±4.0 g,P<-0.0001 and 4.1±0.2 cm,P<-0.01). Growth of the SHAMPF group and the matched NX rats was not significantly different. Weight (56.2±5.0 g) and length (3.4±0.2 cm) gains of NX+GH and NX rats were similar, the beneficial effect of GH therapy on growth being observed in only those animals with more severe degrees of uremia. This growth-promoting action resulted from greater food efficiency and not from stimulated food intake. The hypercholesterolemia seen in NX rats, 81±2 mg/dl versus 55±3 mg/dl in SHAMAL (P0.0001), was not increased in the NX+GH group, 87±3 mg/dl. There was a positive and significant correlation between serum cholesterol and serum urea nitrogen values in NX and NX+GH animals. This study suggests that growth impairment of mild CRF is mainly due to malnutrition and is refractory to GH administration. GH therapy improves the growth rate of animals with advanced CRF without aggravating their lipid abnormalities.