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.

Fluid and electrolytes: parenteral fluid therapy.

Parenteral fluid therapy is a basic component of the care of hospitalized infants and children. Clinicians who care for inpatients must be able to assess the need for parenteral fluid therapy and to specify the composition of fluid and rate of administration. Fluid and electrolyte problems can be challenging but generally can be "tamed" by an organized approach, application of a few principles of physiology, and careful monitoring of the patient. It can be useful to consider separately the amount of fluid needed and the electrolyte composition for maintenance needs, deficit, and ongoing losses. Because maintenance is not as directly related to weight as deficit or as directly measureable as ongoing losses, it tends to cause the most confusion. It will, therefore, be discussed first and in more detail than deficit or ongoing losses.

The AAP practice parameter on urinary tract infections in febrile infants and young children. American Academy of Pediatrics.

The Committee on Quality Improvement of the American Academy of Pediatrics developed an evidence-based practice parameter on the diagnosis, treatment and evaluation of the initial urinary tract infection in febrile infants and young children, two months to two years of age. The practice parameter consists of 11 recommendations and four areas for future research. Recommendations 1 through 5 address diagnosis and emphasize the need for culturing appropriately collected specimens; diagnosis should not be based on urinalysis or on culture of specimens from urine-collection bags. Recommendations 6 through 10 address treatment, identifying trimethoprim-sulfamethoxazole as superior to amoxicillin and establishing the duration of treatment as seven to 14 days. Children should receive antimicrobial coverage until imaging studies have been completed. Recommendation 11 addresses imaging; all infants should undergo ultrasonography, and a lower tract study is strongly encouraged as well. Future research should quantitatively address the relationship between renal scarring in childhood and renal impairment and hypertension in adults. Less invasive methods of diagnosis and imaging are highly desirable and should be developed.

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.

Interim results of a randomized trial of mitomycin C as an adjunct to radical radiotherapy in the treatment of locally advanced squamous-cell carcinoma of the cervix.

The purpose of this study was to determine the efficacy of mitomycin C as an adjunct to radiotherapy for the treatment of locally advanced cervix cancer. Patients with squamous-cell carcinoma of the cervix, stages IB2-IVA, were randomized to receive radiotherapy alone or radiotherapy with concomitant mitomycin C. An initial cohort of 160 patients, having a mean follow-up of 46 months, is analyzed. Intravenous mitomycin C, 15 mg/M(2), was given on the first and sixth week of radiotherapy. The 78 patients in the radiotherapy with mitomycin C group and 82 patients in the radiotherapy alone group have a comparable distribution by age and stage (mean age 47 years; stage IB 3%, IIA 11%, IIB 48%, IIIA 1%, IIIB 36%, IVA 3%). The four-year actuarial survival rates for radiotherapy with mitomycin C and radiotherapy alone were 72% and 56%, respectively (P = 0.13). The four-year actuarial disease-free survival rates for radiotherapy with mitomycin C and radiotherapy alone were 71% and 44%, respectively, a statistically significant difference (P = 0.01). The four-year actuarial local recurrence-free survival rates for patients receiving radiotherapy with mitomycin C and radiotherapy alone were 78% and 63%, respectively (P = 0.11). Differences in four-year distant recurrence-free survival between radiotherapy plus mitomycin C and radiotherapy alone were significantly different at 85% vs. 61% (P = 0.01); this analysis is not adjusted for local failure. On subgroup analysis, stage III-IVA patients had a four-year actuarial disease-free survival of 75% for radiotherapy plus mitomycin C compared with 35% for radiotherapy alone (P = 0.03). There were no treatment- related deaths. Mild hematologic toxicity was seen only in the group treated with mitomycin C. No excess in non-hematologic toxicity has been observed thus far with combined mitomycin C and radiotherapy. In this open phase III trial of mitomycin C as an adjunct to radical radiotherapy for squamous-cell carcinoma of the cervix, there were minimal hematologic effects and no increase in acute radiation reactions. A statistically significant difference in favor of patients receiving mitomycin C is shown for disease-free survival. Thus far, there are trends in favor of those patients receiving mitomycin C for survival and local control. Patients with more advanced stage disease, predominantly stage IIIB, appear to have the most benefit. These preliminary results support the hypothesis that targeting hypoxic cells may lead to a therapeutic enhancement in the radiotherapy of cervix cancer. This trial continues to accrue patients and follow-up data. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 206-223 (2000).

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.

The epidemiology and clinical presentation of urinary tract infections in children younger than 2 years of age.

UTI in young infants generally presents with fever. Among the youngest infants, boys and girls are equally affected. The incidence of UTI in uncircumcised boys is comparable with that in girls, whereas the rate in circumcised boys is much lower. Based on gender and race, white girls have the highest incidence of UTI. A full understanding of the epidemiology of UTI is complicated by the presence of asymptomatic bacteriuria and by incomplete evidence regarding the significance of scarring and the risk of sequelae.

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.

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.

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.

The University of Massachusetts Medical Center office-based continuity experience: are we preparing pediatrics residents for primary care practice?

OBJECTIVE: Surveys of residency graduates and employers have suggested that residency programs do not prepare residents well for practice. Since 1988, pediatric residents at the University of Massachusetts have been paired one-on-one with an office-based pediatrician for their 3-year continuity experience. This survey was conducted to determine if graduates of such a program are prepared to enter pediatric practice. METHODOLOGY: Graduates of the program from 1991 through 1995 who entered primary care practice were surveyed about their preparedness for practice. The questionnaire was also sent to the residents' first employers. The 32 questions were directed to overall sense of preparedness, ability to manage the pace of practice, common illnesses, common behavior problems, anticipatory guidance, office management, and subspecialty problems. RESULTS: Data from all 25 residents who entered practice and the employers of 20 of the 25 residents were obtained and analyzed. Both groups rated overall resident preparedness to be "well-prepared" or "very well-prepared" and gave high scores on working at the pace of practice, diagnosing and treating common illnesses, diagnosing and treating common behavior problems, and providing anticipatory guidance. Areas in which residents were considered to be less well-prepared included anticipatory guidance about nutrition, managing problems by telephone, office management, gynecology, and orthopedics. CONCLUSIONS: The results suggest that continuity experiences in office practices are associated with preparation for the pace and types of visits that occur commonly in primary care practice, abilities which previous surveys of residency alumni and employers have found lacking. Some areas may benefit from a formal curriculum which may be implemented in the office practice, at the medical center, or at both sites. Preceptors may benefit from faculty development and continuing medical education that is directed not only at teaching skills but also at content areas which were not addressed in their own residencies.

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.