The effect of microscopic margin status on survival in adult retroperitoneal soft tissue sarcomas.

INTRODUCTION: Resection is the primary treatment for retroperitoneal (RP) soft tissue sarcomas (STS). Whether obtaining microscopically negative margins (R0) improves overall survival (OS) over microscopically positive margins (R1) remains unclear. METHODS: Using the National Cancer Data Base, we identified adult patients diagnosed with RP STS after R0 or R1 resection from 1998 to 2011. We used a multivariable logistic regression model to identify clinicopathologic factors associated with margin status, including radiotherapy receipt. To assess differences in OS, the log-rank test, Cox proportional hazards regression, and propensity score matching were used. RESULTS: We identified 4015 patients; 2593 (64.6%) underwent R0 resection and 1422 (35.4%) underwent R1 resection. The most common histology was liposarcoma (2,371, 59.1%), median age was 60 years, and median follow up was 67 months. Median OS for R0 vs. R1 patients was 92 and 70 months, respectively (log-rank p < .001). Pre-operative RT was associated with increased probability of R0 resection (68.0% vs. 57.2%, p = .012). Multivariable regression showed R0 vs. R1 resection (HR 0.70, 95% CI 0.60-0.81, p < .001) was associated with improved survival, a finding confirmed on propensity score matching. Other significant predictors of OS included low tumor grade, younger age, smaller tumor size, liposarcoma histology, and receipt of RT (HR 0.81, 95% CI 0.70-0.93, p = .016). CONCLUSIONS: Patients who undergo R0 resection for RP STS appear to experience superior OS compared with patients who had R1 resections.

Second solid tumors in patients with Hodgkin's disease cured after radiation or chemotherapy plus adjuvant low-dose radiation.

PURPOSE: Late solid tumors (STs) are a significant cause of morbidity and mortality in long-term survivors of Hodgkin's disease. To investigate the carcinogenic potential of two different therapeutic approaches, we measured the relative risk (RR) of STs in patients with early-stage disease cured after primary full-dose (approximately 40 Gy) radiation therapy (RT) and in patients with advanced disease who were treated with chemotherapy followed by low-dose (15 to 30 Gy) involved-field radiation (CMT). PATIENTS AND METHODS: Because therapy-induced STs generally begin after a latency period of 5 to 10 years, we restricted our analysis to patients treated before 1986 who achieved durable remissions. Patients who required salvage chemotherapy or who died of Hodgkin's disease were excluded from analysis. The RR of STs was calculated by dividing the observed number of cases by the expected number in a matched population from the Connecticut Tumor Registry. The actuarial incidence of STs was also measured. RESULTS: A total of 197 patients formed the RT group and 116 the CMT group. The median follow-up period in the RT group was 12.8 years, versus 13.5 years in the CMT group. The overall RR of STs in the CMT group was 1.5 (95% confidence interval [CI], 0.6 to 3.5; P = .122). There were no cases of lung or breast cancer. In the RT group, the overall RR of STs was 3.3 (95% CI, 2.0 to 5.3; P < .001). There were seven cases of lung cancer (RR = 10.8; 95% CI, 5.3 to 22.2; P < .001) and two cases of breast cancer (RR = 2; 95% CI, 0.6 to 7.4; P = .07). All six benign tumors occurred in the RT group. CONCLUSION: In patients cured by initial treatment for Hodgkin's disease, RT was associated with a statistically significant increase in STs, particularly lung cancer. CMT was not associated with a significant increase in STs. These data may have important implications for the design of newer therapies for early-stage Hodgkin's disease.

HIV-associated autoimmune hemolytic anemia: report of a case and review of the literature.

While anemia and a positive direct anti-globulin test are each frequently observed in the clinical syndrome of human immunodeficiency virus (HIV) infection, autoimmune hemolytic anemia has rarely been reported in this setting. A case of severe warm autoimmune hemolytic anemia (AIHA) with reticulocytopenia in a patient with AIDS-related complex is reported. Laboratory and clinical findings of severe hemolysis were present, including anhaptoglobinemia, microspherocytosis, splenomegaly, and transfusion dependence. Azidothymidine (AZT) therapy may have exacerbated this patient's anemia. Splenectomy produced a delayed but complete remission of the AIHA despite continuation of AZT therapy. Review of other reports of positive direct antiglobulin tests and autoimmune hemolytic anemia in patients with HIV infections suggests that autoantibodies may be a significant cause of anemia in this population and that the frequent lack of reticulocytosis, despite bone marrow erythroid hyperplasia, may lead to the underdiagnosis of AIHA in HIV-infected patients.

Natural history of cerebral complications of coronary artery bypass graft surgery.

We reviewed 1,669 patients who survived coronary artery bypass graft surgery between 1969 and 1981. A total of 75 cerebral complications were identified, including (1) altered mental state, (2) stroke, and (3) seizure in 64 patients (3.8%). Altered mental state (delirium, hypoxic-metabolic encephalopathy) occurred in 57 (3.4%). Postoperative arrhythmias were associated with an increased risk of altered mental state. Cerebral infarction occurred in 13 (0.8%). Patients who suffered stroke had a higher occurrence of carotid bruits and history of peripheral vascular disease. Seizures occurred in five patients (0.3%). Mortality in patients with a neurologic complication was 29%.

A comparison of the direct and indirect leukocyte migration tests in man.

In the Direct Leukocyte Migration Test, as few as 10% mononuclear cells are sufficient to produce antigen-specific inhibition of polymorphonuclear leukocyte migration in the presence of 100 mug of excipient-free PPD per ml. A clear distinction between tuberculin-positive and tuberculin-negative donors can be made. The inhibition of migration is blocked by the presence of actinomycin D. In the Indirect Test, significant inhibition of migration of pure polymorphs is produced by supernatants from stimulated tuberculin-sensitive lymphocyte cultures. Inhibition is maximal at 6 h and is of a similar degree to that obtained in the direct test.

Dosimetric effects of edema in permanent prostate seed implants: a rigorous solution.

PURPOSE: To derive a rigorous analytic solution to the dosimetric effects of prostate edema so that its impact on the conventional pre-implant and post-implant dosimetry can be studied for any given radioactive isotope and edema characteristics. METHODS AND MATERIALS: The edema characteristics observed by Waterman et al (Int. J. Rad. Onc. Biol. Phys, 41:1069-1077; 1998) was used to model the time evolution of the prostate and the seed locations. The total dose to any part of prostate tissue from a seed implant was calculated analytically by parameterizing the dose fall-off from a radioactive seed as a single inverse power function of distance, with proper account of the edema-induced time evolution. The dosimetric impact of prostate edema was determined by comparing the dose calculated with full consideration of prostate edema to that calculated with the conventional dosimetry approach where the seed locations and the target volume are assumed to be stationary. RESULTS: A rigorous analytic solution on the relative dosimetric effects of prostate edema was obtained. This solution proved explicitly that the relative dosimetric effects of edema, as found in the previous numerical studies by Yue et. al. (Int. J. Radiat. Oncol. Biol. Phys. 43, 447-454, 1999), are independent of the size and the shape of the implant target volume and are independent of the number and the locations of the seeds implanted. It also showed that the magnitude of relative dosimetric effects is independent of the location of dose evaluation point within the edematous target volume. It implies that the relative dosimetric effects of prostate edema are universal with respect to a given isotope and edema characteristic. A set of master tables for the relative dosimetric effects of edema were obtained for a wide range of edema characteristics for both (125)I and (103)Pd prostate seed implants. CONCLUSIONS: A rigorous analytic solution of the relative dosimetric effects of prostate edema has been derived for a class of edema characterized by Waterman et al. The solution proved that the dosimetric effects caused by the edema are universal functions of edema characteristics for a given isotope. It provides an efficient tool to examine the relative dosimetric effects of edema for any given edema characteristics and for any isotopes that may be considered for prostate implants.

Radiation dose selection in Hodgkin's disease patients with large mediastinal adenopathy treated with combined modality therapy.

PURPOSE: To determine the effective dose of consolidation radiation in Hodgkin's disease (HD) patients with large mediastinal adenopathy (LMA) treated with combined modality therapy (CMT). METHODS AND MATERIALS: Eighty-three HD patients with LMA receiving CMT between 1983 and 1997 at Duke University and Yale University were identified. Patients underwent complete clinical staging. The staging breakdown was: IA, 4 patients; IB, 1 patient; IIA, 25 patients; IIB, 33 patients; IIIA, 3 patients; IIIB-6 patients; IVA, 2 patients; and IVB, 9 patients. All patients received induction chemotherapy (CT) as follows: MOPP/ABV(D), 31 patients; BCVPP, 15 patients; ABVD, 24 patients; MOPP, 3 patients; and other regimens, 10 patients. Following 6 cycles of CT, patients were restaged and classified as having either complete response (CR) or induction failure (IF). Post-CT gallium scans were obtained in 52 patients. Patients with residual radiographic abnormalities were classified as having CR if they were gallium-negative and clinically well otherwise. Following induction CT, 78 patients had a CR. There were 5 IFs. Consolidation irradiation was administered to all sites of initial involvement in patients who had achieved CR. RT dose varied. Patients were grouped into the following dose ranges: < or = 20 Gy, 12 patients; 20-25 Gy, 24 patients; 25-30 Gy, 30 patients; > or = 30 Gy, 12 patients. RESULTS: Overall survival and failure-free survival were both 76% at 10 years. Of the 78 CR patients, 15 failed. Patterns of failure were in-field alone, 8 patients; out of field alone, 2 patients; and combined, 5 patients. Failure patterns by RT dose were: < or = 20 Gy, 0/12; 20-25 Gy, 7/24; 25-30 Gy, 5/30; > or = 30 Gy, 3/11. There was no apparent correlation between RT dose and subsequent failure. Post chemotherapy gallium scans were helpful in predicting for failure. Of 48 patients in whom the gallium was negative after chemotherapy, there were 6 failures, compared with 9 failures among 30 patients in whom gallium was not done after chemotherapy (p = 0.066). Additionally, patients receiving adriamycin-based chemotherapy regimens had improved outcomes compared to those not receiving adriamycin (p = 0.03.) CONCLUSIONS: These retrospective data suggest that low-dose radiotherapy following CR achieved with induction chemotherapy (particularly when documented with gallium scanning) may be as effective as higher doses for bulky HD at presentation. Phase III trials are necessary for confirmation of this hypothesis.

Effective treatment of stage I uterine papillary serous carcinoma with high dose-rate vaginal apex radiation (192Ir) and chemotherapy.

PURPOSE: Uterine papillary serous carcinoma (UPSC) is a morphologically distinct variant of endometrial carcinoma that is associated with a poor prognosis, high recurrence rate, frequent clinical understaging, and poor response to salvage treatment. We retrospectively analyzed local control, actuarial overall survival (OS), actuarial disease-free survival (DFS), salvage rate, and complications for patients with Federation International of Gynecology and Obstetrics (FIGO) (1988) Stage I UPSC. METHODS AND MATERIALS: This retrospective analysis describes 38 patients with FIGO Stage I UPSC who were treated with the combinations of radiation therapy, chemotherapy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH/BSO), with or without a surgical staging procedure. Twenty of 38 patients were treated with a combination of low dose-rate (LDR) uterine/vaginal brachytherapy using 226Ra or 137Cs and conventional whole-abdomen radiation therapy (WART) or whole-pelvic radiation therapy (WPRT). Of 20 patients (10%) in this treatment group, 2 received cisplatin chemotherapy. Eighteen patients were treated with high dose-rate (HDR) vaginal apex brachytherapy using 192Ir with an afterloading device and cisplatin, doxorubicin, and cyclophosphamide (CAP) chemotherapy (5 of 18 patients). Only 6 of 20 UPSC patients treated with combination LDR uterine/vaginal brachytherapy and conventional external beam radiotherapy underwent complete surgical staging, consisting of TAH/BSO, pelvic/para-aortic lymph node sampling, omentectomy, and peritoneal fluid analysis, compared to 15 of 18 patients treated with HDR vaginal apex brachytherapy. RESULTS: The 5-year actuarial OS for patients with complete surgical staging and adjuvant radiation/chemotherapy treatment was 100% vs. 61% for patients without complete staging (p = 0.002). The 5-year actuarial OS for all Stage I UPSC patients treated with postoperative HDR vaginal apex brachytherapy and systemic chemotherapy was 94% (18 patients). The 5-year actuarial OS for Stage I UPSC patients treated with HDR vaginal apex brachytherapy and chemotherapy who underwent complete surgical staging was 100% (15 patients). The 5-year actuarial OS for the 20 Stage I UPSC patients treated with combinations of pre- and postoperative LDR brachytherapy and postop WART was 65%. None of the 6 surgically staged UPSC patients treated with LDR radiation and WART/WPRT developed recurrent disease. For patients with FIGO Stage IA, IB, and IC UPSC who underwent complete surgical staging, the 5-year actuarial DFS by depth of myometrial invasion was 100, 71, and 40%, respectively (p = 0.006). The overall salvage rate for local and distant recurrence was 0%. Complications following HDR vaginal apex brachytherapy included only Radiation Therapy Oncology Group (RTOG) grade 1 and 2 toxicity in 16% of patients. However, complications from patients treated with WART/WPRT, and/or LDR brachytherapy, included RTOG grade 3 and 4 toxicity in 15% of patients. CONCLUSION: Patients with UPSC should undergo complete surgical staging, and completely surgically staged FIGO Stage I UPSC patients can be effectively and safely treated with HDR vaginal apex brachytherapy and chemotherapy. Both OS and DFS of patients with UPSC are dependent on depth of myometrial invasion. The salvage rate for both local and distant UPSC recurrences is extremely poor. Complications from HDR vaginal apex brachytherapy were minimal.

Educational principles of community-based education.

Much of medical education remains teacher centered, as exemplified by the continued emphasis on lectures. Increasingly, however, the importance of the learner is being recognized and acknowledged in medical school curricula. The distinction between teaching and learning is also an issue for graduate medical education; accreditation bodies focus on programs and teaching, and credentialing bodies determine whether individuals have accomplished sufficient learning. The true mission of teaching is to facilitate learning, and adult learning is enhanced by four elements: respect, building on previous experiences, immediacy of application, and the opportunity to practice. These elements should be considered when designing educational experiences in the community. Educational planning includes five steps, represented by the mnemonic GNOME: goals, needs assessment, objectives, methods, and evaluation. Goals are broad aspirations, which are refined by the learners' needs to specific, measurable objectives. Methods are selected to match the objective, and evaluation determines whether the objectives were achieved. The results of the evaluation serve as another needs assessment, and the process continues until the goals are achieved. Throughout the process, the primary focus should be on the resident, with the program in a supporting role.

The automobile and heat stress.

This study suggests that the thermal burden of poorly ventilated parked automobiles can be considerable, particularly when the automobiles are exposed to direct sunlight. Leaving the windows open two inches does not appear to be protective. The pratice of exposing infants and toddlers to such thermal risk appears to be common and the need for adequate ventilation unrecognized. Education measures stressing the use of carseats and other safety devices should include the potential hazards of high temperature in parked automobiles.

A successful city-wide smoke detector giveaway program.

Each year, 5,000 Americans die and 300,000 are hospitalized as a result of 2.8 million residential fires. Almost all house fires allow time for safe exit if an early warning is given. Smoke detectors are an effective, reliable, and inexpensive method of providing such warning. After an upsurge of deaths related to fires in 1982, Baltimore City gave away 3,720 smoke detectors to households that requested them. This study addressed two questions: (1) Did the households that received the smoke detectors install them? (2) Was the population reached by this giveaway program a population at high risk from fire? A survey of 231 randomly selected households among those requesting smoke detectors was conducted 8 to 10 months after the giveaway program. At that time, smoke detectors were installed in 92% (212/231) of the homes and 88% (187/212) of the installed smoke detectors were operational. Households requesting smoke detectors were in census tracts at higher risk from fire. The correlation coefficient between the rate of requesting a smoke detector and the risk of death or injury related to fires was r = .90, P less than .001. The 231 surveyed households had more personal fire risk factors than the general population. The success of this smoke detector giveaway program is notable in that it required the active participation of a high-risk population.

Relation between radionuclide angiographic regional ejection fraction and left ventricular regional ischemia in awake dogs.

Multigated equilibrium radionuclide angiography was used to quantitate global and regional ejection fraction (EF) in 26 awake dogs 10 minutes after distal and then proximal occlusion of the left anterior descending (LAD) or left circumflex (LC) coronary artery. Changes in global and regional EF were correlated with simultaneous measurements of the extent of acute left ventricular (LV) ischemia measured by radioisotope-labeled microspheres. The extent of ischemia, defined as the percentage of LV mass with greater than 25% reduction in blood flow from normal regional flow, was linearly related to the percent change in global EF after LAD (r = 0.84) and LC (r = 0.77) occlusions. The extent of ischemia also correlated with regional EF (r = 0.47 to 0.88 for LAD and r = 0.41 to 0.69 for LC occlusions). In 24 of 25 LAD occlusions and in all 20 LC occlusions that produced a measurable ischemic zone, the maximal percent change in regional EF exceeded the percent change in global EF. Two LAD occlusions and 2 LC occlusions reduced regional EF but not global EF. Thus, global and regional EF decreased in direct proportion to the extent of acute myocardial ischemia; regional ischemia produced greater changes in regional than in global EF.

Cyclophosphamide, cytosine arabinoside and TBI as a conditioning regimen for allogeneic bone marrow transplantation in patients with leukemia.

This is a prospective study designed to determine the toxicity, efficacy and antileukemic effect of high-dose cytosine arabinoside (ara-C), cyclophosphamide and total body irradiation (TBI) as a myeloablative regimen prior to allogeneic bone marrow transplantation for patients with hematologic malignancies. Fifty-eight patients with hematologic malignancies were treated with cyclophosphamide, high-dose ara-C and total body irradiation (TBI) followed by allogeneic bone marrow transplantation. Fifty patients had good prognosis disease and eight had poor prognosis disease. Cyclosporine and short-course methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. The conditioning regimen consisted of ara-C 3000 mg/m2 twice a day x six doses on days -7, -6, and -5; cyclophosphamide 1800 mg/m2 on days -4 and -3; and TBI 1400 cGy midline dose at 5 cGy/min in eight total fractions administered twice a day on days -4, -3, -2, and -1. The bone marrow was infused on day 0 (zero). Toxicity related to the conditioning regimen was comparable to that reported with other conditioning regimens, except for diarrhea which appears to be more frequent. The actuarial survival at 1 year was 69% (58-82) and at 5 years was 54% (42-69) with the numbers in parentheses representing the 95% confidence interval of the Kaplan-Meier estimate. After a median follow-up of 28 months, 31 of 58 (53%) patients are alive without evidence of disease. Only four of the 58 patients (7%) have relapsed. Cyclophosphamide, ara-C and TBI is a safe and effective myeloablative regimen for patients with leukemia. The overall relapse rate in our study was 7% with a median follow-up of 28 months and appears to be lower than relapse rates reported in other series. This is probably due to the added antileukemic effect of ara-C. This regimen should be compared with other myeloablative regimens in a controlled study.

Teaching residents about patient and practice termination in community-based continuity settings.

BACKGROUND: The pediatric residency program at the University of Massachusetts Medical Center, Worcester, has based its continuity experience in community practices since 1988. Residents develop a relationship not only with their patients but also with the preceptors, with whom they are paired one-on-one, and with office staff. OBJECTIVE: To describe the structure and results of an educational program that was developed to address the termination issues that arise at the end of residency. The educational program consists of four components: (1) a seminar, (2) a "mini-block" rotation, (3) office staff involvement, and (4) a resident-preceptor dinner. RESULTS: The following issues and themes have been recurrent in the discussions during the past 4 years: (1) the importance, for patient and resident, of identifying who will be the subsequent health care provider for the patient; (2) the inability to identify which patients had strongest attachment to residents; (3) parental surprise about the resident's departure, even though all parents had been told that the resident was going to be in the practice for only a limited period; (4) the desire of residents to have follow-up on patients after termination; (5) critical aspects of the process of informing patients about the resident's departure; (6) the importance of identifying and addressing the attachment of the resident to the preceptor and office staff, as well as to patients; and (7) the affirming experience that the termination sessions with the patients can be for the residents. CONCLUSION: Although the termination process is potentially emotionally difficult, it can be a personally and educationally valuable experience for residents.

A program to develop residents as teachers.

Residents are recognized as important and influential teachers of medical students. Although they are expected to teach and evaluate students, few residents have been taught how, and most would like to receive training to develop and improve their skills as teachers. We developed a "Residents as Teachers" retreat based on our faculty development program for clinical preceptors. We focused on clinical precepting skills, including evaluation/feedback, and the ability to prepare and deliver a brief presentation. The program increased knowledge and skills and improved attitudes about teaching, as reflected in self-reports, observed performance, and medical student ratings. The retreat also provided a valuable social experience for residents. The program has been considered beneficial by residents, program faculty members, medical students, the student clerkship director, and the residents' primary care preceptors. The retreats form the centerpiece of our curriculum for residents as teachers and have become an annual tradition in the residency program.

Combined chemotherapy and radiotherapy for Hodgkin's disease.

This paper reviews the treatment of advanced and intermediate stage Hodgkin's disease with combination chemotherapy alone and combined chemotherapy and radiation. Relapse following complete remission with chemotherapy occurs principally at initial sites of disease; its occurrence will be reduced by radiotherapy to those sites. There is disagreement regarding the frequency of relapse and hence the impact of consolidation radiotherapy. Our interpretation of the literature is that relapse occurs in approximately 25% to 50% of all patients achieving complete response with chemotherapy, and that consolidation radiation reduces relapse frequency with a resultant increase in survival. The addition of low dose, involved field radiotherapy is generally free of significant adverse effects. In particular, there appears to be no increase in second malignant neoplasms. The risk: benefit ratio for adding radiotherapy to chemotherapy in patients with advanced Hodgkin's disease is, therefore, quite favorable. We believe that combined modality therapy should become the standard treatment.

Pediatrics in the community hospital.

The subject of the community hospital's pediatric service-its mission, organization and staff-is ripe for critical study and innovative implementation. The centripetal force of medical education which has kept the best medical school graduates within the tertiary hospital walls during medical school, residency, fellowship, and subspecialty practice has had a perhaps unintended though real inhibiting effect on the community hospital. Those who practice in the community environment may well be less equipped to study and change their world than are their academic counterparts. They often lack the training to do so, and lack time that can be taken from busy practice commitments. Those most capable of critical study are unfamiliar with or at least not always empathic to the community's problems. We suggest that there are many clinical questions and many organizational issues that are legitimate matter for study within community hospitals, in which a majority of the nation's children are cared for. The increasing number of affiliations between university and community hospitals may allow a true academic bond to develop and learning to occur at both ends. The community hospital has both the need and potential for important growth in the 1980s.

Clinical teaching improvement: past and future for faculty development.

Faculty development programs have focused on the improvement of clinical teaching for several decades, resulting in a wide variety of programs for clinical teachers. With the current constraints on medical education, faculty developers must reexamine prior work and decide on future directions. This article discusses 1) the rationale for providing faculty development for clinical teachers, 2) the competencies needed by clinical teachers, 3) the available programs to assist faculty to master those competencies, and 4) the evaluation methods that have been used to assess these programs. Given this background, we discuss possible future directions to advance the field.

Infectious mononucleosis in adolescents.

Infectious mononucleosis is a clinical manifestation of primary EBV infection in adolescents, characterized by a triad of clinical, laboratory, and serologic features. The classic signs and symptoms are not seen in every patient; rather, the presentations tend to fit into one of three clinical forms (pharyngeal, glandular, or febrile). Recognizing these syndromes provides a useful framework for anticipating the clinical course, complications, and differential diagnosis. Nonclassic presentations of IM include a wide variety of neurologic abnormalities, thrombocytopenic purpura, and splenic rupture. The laboratory features of IM include absolute lymphocytosis with a large percentage of atypical lymphocytes, and abnormal liver chemistries in 90% of patients. The diagnosis of IM is confirmed serologically, usually with the demonstration of heterophile antibodies; the test can conveniently be performed in office laboratories. If the heterophile antibody test is negative, EBV-specific serologic tests can identify whether the illness is due to primary EBV infection. Once the diagnosis of IM is made, appropriate guidelines for resumption of activity should be provided to patients, especially to those with evidence of splenomegaly. Medical management includes supportive therapy with adequate analgesia. Corticosteroids are indicated for patients with upper airway obstruction; they may be helpful in patients with neurologic, hematologic, or cardiac complications. Acyclovir may prove to be useful, but further studies are needed before its use can be recommended.