The role of adjuvant chemotherapy in the treatment of adult soft tissue sarcomas

The influence of the postantibiotic effects (PAEs) of ciprofloxacin, pefloxacin, imipenem, meropenem and amikacin in the suprainhibitory concentrations (2 x and 4 x MIC) on the metabolic processes of P. aeruginosa was studied. The synthesis of macromolecules was expressed by influencing of the incorporation rate of [14C] adenine and [14C] leucine. Remarkable affecting of both biosynthetic processes evoked the suprainhibitory concentration 4 x MIC of meropenem by inhibition of the nucleic acids synthesis to 76.1% and proteins synthesis to 61.1% against the control. The suprainhibitory concentration 4 x MIC of both pefloxacin and ciprofloxacin affected the highest suppression of the endogenous respiration to 16.5% and to 20.3%, respectively. The respiration was influenced the least after the effect of meropenem in the both suprainhibitory concentrations tested. According to our knowledge, this is first report about the evaluation of the endogenous respiration after PAE. In this study we demonstrated the inhibitory effects of 4 x MIC concentration of antibiotics studied on the metabolic processes of P. aeruginosa. The results suggest a multiple mechanism for the PAE.     

High-dose epirubicin is not an alternative to standard-dose doxorubicin in the treatment of advanced soft tissue sarcomas. A study of the EORTC soft tissue and bone sarcoma group

The activity and toxicity of single-agent standard-dose doxorubicin were compared with that of two schedules of high-dose epirubicin. A total of 334 chemonaive patients with histologically confirmed advanced soft-tissue sarcomas received (A) doxorubicin 75 mg m(-2) on day 1 (112 patients), (B) epirubicin 150 mg m(-2) on day 1 (111 patients) or (C) epirubicin 50 mg m(-2) day(-1) on days 1, 2 and 3 (111 patients); all given as bolus injection at 3-week intervals. A median of four treatment cycles was given. Median age was 52 years (19-70 years) and performance score 1 (0-2). Of 314 evaluable patients, 45 (14%) had an objective tumour response (eight complete response, 35 partial response). There were no differences among the three groups. Median time to progression for groups A, B and C was 16, 14 and 12 weeks, and median survival 45, 47 and 45 weeks respectively. Neither progression-free (P = 0.93) nor overall survival (P = 0.89) differed among the three groups. After the first cycle of therapy, two patients died of infection and one owing to cardiovascular disease, all on epirubicin. Both dose schedules of epirubicin were more myelotoxic than doxorubicin. Cardiotoxicity (> or = grade 3) occurred in 1%, 0% and 2% respectively. Regardless of the schedule, high-dose epirubicin is not a preferred alternative to standard-dose doxorubicin in the treatment of patients with advanced soft-tissue sarcomas.     

Therapeutic use of carminomycin in soft tissue sarcomas

Under endoscopic control, biopsy specimens were taken from the oxyntic gland area of the stomach before and after administration of pentagastrin, synthetic secretin, and 13-norleucine motilin (13-nle-motilin), respectively. In 29 volunteers, the basal rate of 14C-leucine incorporation into mucosal protein averaged 41.2 +/- 7.7 X 103 cpm/mg protein (mean +/- S.D.). One and 4 hours after s.c. administration of pentagastrin (6 mug/kg body weight), values were significantly increased (p less than 0.05) by 18.9 and 21.8%, respectively, with respect to the basal level. One hour after an intravenous shot of 2 CU per kg body weight of secretin, gastric mucosal protein synthetis was not substantially inhibited, whereas a 1-hour continuous i.v. infusion of 13-nle-motilin (0.4 mug/kg body weight, hr) significantly decreased 14C-leucine incorporation rates by 17.5% (p less than 0.05). In contrast to rats, 1 hour after s.c. pentagastrin, protein synthesis in human duodenal mucosa was not altered. From these results it may be concluded that pentagastrin has a trophic influence on gastric mucosa in man. Moreover, the data presented are compatible with the hypothesis that gastrin and motilin may be involved in the regulation of human gastric mucosal protein synthesis.     

Pulmonary metastasectomy for soft tissue sarcomas: is it justified?

beta-blocker therapy for mitral stenosis is controversial. This study compares right and left heart hemodynamics at rest and supine submaximal exercise in patients (n = 7) receiving chronic beta-antagonists with untreated patients (n = 17) matched for age (mean +/- SD = 51 +/- 12 years) and valve area (0.7 +/- 0.2 cm2/m2). Little benefit was observed with treatment at rest. Although pulmonary capillary wedge pressures (PCWP) were lower during exercise in the beta-blocker group (22 +/- 4 vs. 31 +/- 9 mmHg; P < 0.05), exercise performance was not enhanced and cardiac output response during exercise was reduced (control = 41% increase vs. 12% for beta-blockade). PCWP rose rapidly when diastolic filling periods were < 300 msec in both groups. Pulmonary capillary wedge pressure was found to be a nonlinear functions (P < 0.001) of diastolic filling period (PCWP = 15.9 + 5.84 x 10(5)/dfp2). These data suggest that there is a critical heart rate in patients with mitral stenosis above which hemodynamic compromise rapidly occurs.     

Surgical aspects in the multidisciplinary treatment of soft tissue sarcomas

Sarcomas are rare malignant tumors with a large variety of histologic subtypes. The surgical approach depends more on the histologic grade, the size and the site of the tumor. Radiologic diagnosis relies predominantly on MR-imaging. Discernible improvements have taken place in soft tissue sarcoma patient survivorship and quality of life over the past 20 years, with overall 5-year survival currently at approximately 50-80%. The place of surgery in the treatment of soft-tissue sarcoma is defined in the light of a review of the recent literature. Radical surgical resection is the mainstay of therapy. Local recurrence is the most common type of failure. Local recurrence is resectable and limb preservations possible in the majority of patients. Survival after treatment of local recurrence is determined mainly by the grade and secondarily by the size of the tumor. The essential risk factor for local recurrence is the quality of surgical resection, defined by the definitive resection margins. A lateral safety margin of 5 cm and of 2 cm to the depth should be respected. In sarcoma of the extremity the compartment is defined based on clinical, radiographic, histopathologic and operative findings. The use of muscle flaps to fill the surgical defects can improve the functional result and reduce the complication rate. Only about 5% of the patients need amputation. Evaluation of functional results must be based on objective criteria. In retroperitoneal sarcoma the significant factors for determining prognosis are grade and completeness of exzision. Multidisciplinary treatment according to common protocols is essential. Shifts in treatment have taken place over the past decade, from single-modality treatment involving radical surgery with compartment resection to sophisticated limb-salvage strategies combined with radiation therapy. In case of inadequate surgery e.g. in a large tumor with positive margins in high-grade soft tissue sarcomas the addition of radiotherapy can improve local control, but cannot ensure that obtained by adequate surgery. Patients with large (greater than 5 cm), high grade soft tissue sarcoma are at high risk for distant recurrence and disease-related mortality. Investigations of combined modality therapy with newer chemotherapy agents and dose intensification treatment strategies are warranted.     

Missing data: Our view of the state of the art.

Statistical procedures for missing data have vastly improved, yet misconception and unsound practice still abound. The authors frame the missing-data problem, review methods, offer advice, and raise issues that remain unresolved. They clear up common misunderstandings regarding the missing at random (MAR) concept. They summarize the evidence against older procedures and, with few exceptions, discourage their use. They present, in both technical and practical language, 2 general approaches that come highly recommended: maximum likelihood (ML) and Bayesian multiple imputation (MI). Newer developments are discussed, including some for dealing with missing data that are not MAR. Although not yet in the mainstream, these procedures may eventually extend the ML and MI methods that currently represent the state of the art. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Operative management of soft tissue sarcomas: impact of anatomic site

Operative management of soft tissue sarcomas begins with the surgical biopsy. Incisional biopsy of an undiagnosed soft tissue mass allows optimal later definitive resection, this resection including the entire biopsy wound, as well as accomplishing an "adequate" margin around the sarcoma. The principles employed for this resection are those that lead to adequate gross and microscopic margins of normal tissue around the sarcoma while considering the limitations, in terms of physical disability, from the procedure itself. This operative strategy is described for various anatomic locations, such as the extremities, trunk, retroperitoneum, and head and neck; special problems with each of these primary sites are discussed.     

S-phase fraction of 155 soft tissue sarcomas: correlation with clinical outcome

BACKGROUND: Traditionally, grade is considered the most important prognostic factor for soft tissue sarcomas (STS). However, because of the alleged difficulties in reproducibility of grading, new, objectively determined prognostic factors would be of value. The aim of our study was to establish if S-phase fraction (SPF) measured with flow cytometry was of prognostic significance for STS. METHODS: In this study, we included all 193 adult STS patients with superficial trunk or limb tumors who were treated by the Helsinki University Central Hospital (HUCH) STS group between January 1987 and May 1993. One hundred and seventy-two formalin fixed paraffin embedded tumor samples were available. SPF measurement was successful in 155 cases. RESULTS: Eighty-six cases were diploid. Ploidy was found to have no effect on overall survival. The median SPF was 6.8% (diploid tumors, 4% and nondiploid tumors, 12.9%). A high SPF predicted a shorter survival in patients with diploid tumors (P=0.003). The prognostic value was even stronger when we studied disease specific survival and excluded from analysis samples that contained less than 50% tumor cells (P=0.011). However, no prognostic value could be detected in nondiploid tumors or in the material as a whole. CONCLUSIONS: Our results suggest that high SPF is an adverse prognostic factor for survival of patients with diploid STS. However, further studies are needed to confirm these results.     

Phase II study of rapid-scheduled etoposide in paediatric soft tissue sarcomas

Twenty three patients with paediatric soft tissue sarcomas who had relapsed or refractory disease were treated with a rapid schedule of intravenous etoposide (100 mg/m2 daily on three consecutive days, weekly over 3 weeks). The regimen was well tolerated with predictable myelotoxicity. In 19 patients with rhabdomyosarcoma, there was a response rate of 42%. This appears to be better than previously reported with conventional three weekly schedules. These data indicate that for rhabdomyosarcoma, as for some other tumours, a divided dose regimen may be the optimal schedule and is worthy of further evaluation.     

Surgical management of soft tissue sarcomas: principles of resection and reconstructive plastic procedures

1. Adequate complete surgical resection with a oncologic radical or wide margin of normal tissue represents the most important measure to prevent a local recurrence. Limited excision with "shelling-out" of the tumor, through its "pseudocapsule" almost invariably means positive microscopic margins. The pathohistologically or macroscopically marginal or intralesional positive resection margins make a salvage surgery necessary. 2. A close safety margin of < 1 cm due to neighboured anatomic structures indicates a high risk of local recurrence and makes an adjuvant radiotherapy mandatory. Plastic-reconstructive surgery should prepare the radiotherapy fields, to avoid cavities or ulcerations. 3. Facts should be stated in the clinical record and the operation report, e.g. the safety margin should be defined by the surgeon and the pathologist; the histopathologic stage and grade are absolutely basic requirements. If necessary, a second histopathologic review should be asked for. 4. Tumor resection and reconstructive oncoplastic measures should correspond individually to the oncologic parameters, to the functional demands and to the age of the patient. 5. Multidisciplinary cooperation in a tumorboard is a precondition for an adequate treatment.     

The art of Pirandello: a psychoanalytic view

Luigi Pirandello, a playwright of immense profundity and creativity, won the Nobel Prize for his work in theater. A brief history of his personal and educational development is presented here, followed by an excellent translation by Gigi Gatti and Terry Doyle of one of his plays, The Man with the Flower in His Mouth, written in 1926. It is a play that is little known in the United States, but which conveys his style and many of his views in a succinct manner. This is followed by an interpretation of some of the symbols, the psychodynamics, and the ego states of the characters that Pirandello described before those ego states were described in psychoanalytic literature.     

Adjuvant chemotherapy for primary cardiac sarcomas: the IGR experience

The effect of additional treatments after surgery in patients with primary cardiac sarcoma (PCS) remains unknown. The present study aims to evaluate the benefit of chemotherapy in patients with non-metastatic cardiac sarcomas after optimal resection. Between October 1979 and December 1995, 15 patients with a median age of 45 (range 16-66) and a resected primary cardiac sarcoma [angiosarcoma (six), malignant fibrous histiocytoma (three), leiomyosarcoma (two), rhabdomyosarcoma (two), liposarcoma (one) and synoviosarcoma (one)] received a doxorubicin-containing regimen within 6 weeks of surgery. Adjuvant chemotherapy combinations included cyclophosphamide, vincristine and dacarbazine in four patients; ifosfamide in nine; methotrexate and vincristine in one; and doxorubicin alone in one patient. At present, 13 patients have relapsed (five during therapy), with a median time to progression of 10 months. Twelve patients developed local relapse, in four cases without metastatic disease. Two patients remain in complete remission 27 and 25 months after surgery. The median time to progression was shorter in patients presenting a cardiac angiosarcoma than other histological types (3 vs 14 months, P < 0.01). Twelve patients have died, with a median overall survival of 12 months. The 2-year survival rate is 26%. Survival was significantly longer for patients with completely resected tumours (22 vs 7 months; P = 0.02) and those who did not have angiosarcoma (18 vs 7 months; P = 0.04). In conclusion, post-operative conventional doxorubicin-based chemotherapy failed to modify the natural history of patients with resected cardiac sarcomas. Locoregional failure remains the main problem even after histologically complete resection. New approaches must be tested in patients with primary cardiac sarcoma.     

High-dose ifosfamide plus adriamycin in the treatment of adult advanced soft tissue sarcomas: is it feasible?

BACKGROUND: Adriamycin (ADM) and ifosfamide (IFO) are the two most active agents in the treatment of soft tissue sarcomas (STS) with a clear dose-response relationship. We evaluated the feasibility and toxicity of a high-dose IFO-plus-ADM combination. PATIENTS AND METHODS: Fourteen patients with advanced disease and nine patients in adjuvant setting received IFO 12.5 g/m2 in 120-hour continuous infusion with Mesna uroprotection and ADM 20 mg/m2 on days 1-3 and G-CSF every three weeks. RESULTS: Twenty-three patients received 89 chemotherapy cycles (70 cycles at full dose). Seventeen patients received the planned treatment, and nine patients required dose reductions. We observed grade 3-4 neutropenia in 52 cycles (59%)/20 patients; grade 3-4 thrombocytopenia in 16 cycles (18%)/nine patients; grade 3-4 anaemia in 24 cycles (27%)/11 patients. Eight patients experienced febrile neutropenia and six patients required blood transfusions. CONCLUSIONS: While feasible, this regimen showed heavy toxicity. Nevertheless, 74% of the patients were able to complete the planned treatment. Adjustment of the schedule of IFO continuous infusion to improve this combination is currently under investigation.     

Mental health services for children: The state of the art.

Throughout this century, people in the United States have been concerned about the serious deficiencies in the mental health care of our children. Despite eloquent needs assessment and recommendations for remediation, most of the unserved needs and deficiencies of our mental-health-care-delivery system remain the same. This article reviews the current status of mental health services to children, youth, and families to highlight the necessity of an integrated system of mental health care. The development of a continuum of care that is coordinated across the mental health and non-mental-health systems that naturally occur in all children's lives has the potential to vastly improve mental health services to children, youth, and families. (PsycINFO Database Record (c) 2010 APA, all rights reserved)