Using standardized patients to teach end-of-life skills to clinical clerks.

BACKGROUND: This study examines the use of standardized patients to teach end-of-life skills to clinical clerks. METHODS: Forty-four third-year clinical medical students participated in a half-day standardized patient workshop that was precepted by faculty members. The students were asked to report on their perceived abilities prior to the workshop and these were compared with post-workshop responses. The students were also asked to provide an overall evaluation of the standardized patient workshop as a learning experience. RESULTS: The students uniformly found the workshop to be realistic, found the faculty facilitators to be helpful, and found the workshop effective in enhancing their end-of-life skills. Following participation in the workshop, students reported significant improvements in their perceived abilities to deal with pain, to appreciate cultural differences in the dying process, to deliver bad news, and to understand the legalities of do-not-resuscitate orders. CONCLUSIONS: Standardized patient workshops are useful for teaching end-of-life skills.

Acute treatment-related diarrhea during postoperative adjuvant therapy for high-risk rectal carcinoma.

PURPOSE: The combination of pelvic radiotherapy and 5-fluorouracil-based chemotherapy is associated with an increase in acute gastrointestinal toxicity during rectal adjuvant therapy, most notably an increased incidence of diarrhea. Previous randomized, prospective studies have limited their analysis to presenting rates of severe and life-threatening diarrhea (Grade 3 or greater), and few data are available detailing the extent of mild to moderate diarrhea. To provide baseline data for future studies, we conducted a detailed analysis of diarrhea from a prior clinical trial of adjuvant therapy for rectal cancer. METHODS AND MATERIALS: In a multiinstitutional clinical trial, 204 eligible patients with rectal carcinoma that either was deeply invasive (T3-T4) or involved regional lymph nodes were randomized to receive either postoperative pelvic radiotherapy alone (45 to 50.4 Gy) or pelvic radiotherapy and bolus 5-fluorouracil-based chemotherapy. Toxicity was assessed prospectively. RESULTS: For the 99 eligible patients who received pelvic radiotherapy alone, rates of Grades 0, 1, 2, 3, and 4 diarrhea during treatment were 59, 20, 17, 4, and 0%, respectively. For the 96 eligible patients who received radiotherapy and 5-fluorouracil, the overall rates of grades 0, 1, 2, 3, and 4 diarrhea were 21, 34, 23, 20, and 2%, respectively. The increased rates of diarrhea during adjuvant rectal therapy were manifested across all toxicity levels for patients receiving chemotherapy and pelvic radiotherapy. Of primary clinical importance is the substantial increase in severe or life-threatening diarrhea (Grade 3 or more) (22 vs. 4%,p = 0.001) Additionally, increased rates of any diarrhea and also severe or life-threatening diarrhea were observed in patients who had a low anterior resection compared with those who had an abdominoperineal resection (p < 0.001 and p = 0.006, respectively). CONCLUSION: These results will be of value as a baseline for investigators who want to use treatment toxicity as an end point in cancer control or cancer therapy trials utilizing similar treatment techniques. Patients receiving 5-fluorouracil and pelvic radiotherapy compared with patients receiving pelvic radiotherapy alone and patients with a prior history of a low anterior resection compared with patients who had a prior history of an abdominoperineal resection experienced increased rates of Grades 1 through 4 acute treatment-related diarrhea, and the most important increase occurred as Grade 3 toxicity.

Chemoprevention for colorectal carcinoma.

The literature on chemoprevention for colorectal carcinoma can be summarized as follows: (1) Aspirin and NSAIDs usage can decrease polyp formation and promote polyp regression and have a strong epidemiologic link to colorectal cancer prevention. (2) Fiber intake is strongly associated with a decreased incidence of colorectal carcinoma. Whether supplemental fiber can prevent colorectal neoplasia is not yet clear. (3) Calcium and vitamin D intake is inversely proportional to the risk of developing colorectal carcinoma. Prospective trials make the role of supplemental calcium as a chemoprotective agent unclear: (4) Chemoprevention is an exciting area of research. More work needs to be done to establish the precise steps necessary for neoplastic transformation of cells so that pharmaceuticals can be developed to target carcinogenesis at several levels.

Hepatosplenic gammadelta T-cell lymphoma: ultrastructural, immunophenotypic, and functional evidence for cytotoxic T lymphocyte differentiation.

Hepatosplenic gammadelta T cell lymphoma (TCL) is a rare, aggressive subset of peripheral TCL that presents with hepatosplenomegaly and cytopenias. Detailed clinicopathological, ultrastructural, and cytogenetic analyses of these lymphomas are limited; functional characteristics of these lymphomas are unknown. We have undertaken a clinicopathological, immunophenotypic, ultrastructural, cytogenetic, and functional analysis of three hepatosplenic gammadelta TCLs. All patients presented with massive hepatosplenomegaly and anemia, thrombocytopenia, or severe neutropenia; terminal blastlike transformation occurred in one patient. Combination chemotherapy had no response in two patients, but induced complete remission in one. gammadelta T cell receptor (TCR) expression and clonal TCRdelta gene rearrangements were documented in each case. Two different subsets of gammadelta TCL were identified based on delta chain variable region usage; two lymphomas were Vdelta1+, whereas the third was negative for both Vdelta1 and Vdelta2. Cytogenetic analysis was performed on two lymphomas; isochromosome 7q and probable trisomy 8 was shown in one of the Vdelta1+ lymphomas, whereas the Vdelta1 negative lymphoma had 14p+ with t(1;14)(q21;p13). NK cell-associated antigens (CD11c, CD16, or CD56) and cytotoxic T lymphocyte (CTL) effector proteins (perforin, granzyme B, TIA-1, and Fas ligand) were expressed by each lymphoma; dense core cytolytic granules were observed by electron microscopy in both lymphomas studied. Functional studies performed in two cases showed TCR-mediated cytolysis of P815 x 2 FcR+ cells induced by anti-CD3 in a redirected cytolysis assay in one of the CD56+, Vdelta1+ lymphomas, whereas IFNgamma secretion was induced by anti-CD3 in the CD56-, Vdelta1 negative lymphoma. These studies show that hepatosplenic gammadelta TCLs have CTL differentiation, retain functional activity in vitro, and are derived from at least two gammadelta T cell subsets.

An enhanced prognostic system for clinically localized carcinoma of the prostate.

BACKGROUND: This investigation was conducted to develop an enhanced prognostic system based on readily available and independently predictive tumor-related factors for patients with clinically localized prostate carcinoma. METHODS: The outcome of 500 patients treated solely with irradiation for clinical TNM classifications T1-4, NO or NX, MO prostate carcinoma was used to identify factors independently associated with disease relapse. Logistic regression constructed a risk score equation, and optimized cutoff points to characterize patient groups with low, intermediate, or high risks for relapse were established with receiver operating characteristic curve analysis. RESULTS: Clinical tumor stage (P < 0.00001), Gleason score (P = 0.0002), and pretherapy serum prostate specific antigen (P < 0.00001) were independently associated with clinical or biochemical relapse. These factors were included in a risk score equation that defined patient groups with a distinctly different outcome. For the low, intermediate, and high risk groups, the relapse-free probabilities at 5 years after irradiation were 92%, 67%, and 24%, respectively (P < 0.00001). CONCLUSIONS: Readily available, pretherapy disease-related characteristics formed the basis of an enhanced prognostic system for patients with clinically localized prostate carcinoma. A multivariate prognostic system of this nature estimated patient prognosis in a more exacting fashion than a system exclusively based on anatomic factors.

Genetic testing for susceptibility to adult-onset cancer. The process and content of informed consent.

OBJECTIVE: To provide guidance on informed consent to clinicians offering cancer susceptibility testing. PARTICIPANTS: The Task Force on Informed Consent is part of the Cancer Genetics Studies Consortium (CGSC), whose members were recipients of National Institutes of Health grants to assess the implications of cancer susceptibility testing. The 10 task force members represent a range of relevant backgrounds, including various medical specialties, social science, genetic counseling, and consumer advocacy. EVIDENCE: The CGSC held 3 public meetings from 1994 to 1996. At its first meeting, the task force jointly established a list of topics. The cochairs (G.G. and J.R.B) then developed an outline and assigned each topic to an appropriate writer and reviewer. Writers summarized the literature on their topics and drafted recommendations, which were then revised by the reviewers. The cochairs compiled and edited the entire manuscript. All members were involved in writing this report. CONSENSUS PROCESS: The first draft was distributed to task force members, after which a meeting was held to discuss its content and organization. Consensus was reached by voting. A subsequent draft was presented to the entire CGSC at its third meeting, and comments were incorporated. CONCLUSIONS: The task force recommends that informed consent for cancer susceptibility testing be an ongoing process of education and counseling in which (1) providers elicit participant, family, and community values and disclose their own, (2) decision making is shared, (3) the style of information disclosure is individualized, and (4) specific content areas are discussed.

Recommendations for follow-up care of individuals with an inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Cancer Genetics Studies Consortium.

OBJECTIVE: To provide recommendations for cancer surveillance and risk reduction for individuals carrying mutations associated with hereditary nonpolyposis colon cancer (HNPCC). PARTICIPANTS: A task force with expertise in medical genetics, oncology, primary care, gastroenterology, and epidemiology convened by the Cancer Genetics Studies Consortium (CGSC), organized by the National Human Genome Research Institute (previously the National Center for Human Genome Research). EVIDENCE: Studies evaluating cancer risk, surveillance, and risk reduction in individuals genetically susceptible to colon cancer were identified using MEDLINE and bibliographies of articles thus identified. Indexing terms used were "genetics" in combination with "colon cancer," and "screening" in combination with "cancer family" and "HNPCC." For studies evaluating specific interventions, quality of evidence was assessed using criteria of the US Preventive Services Task Force. CONSENSUS PROCESS: The task force developed recommendations through discussions over a 14-month period. CONCLUSIONS: Efficacy of cancer surveillance or other measures to reduce risk in individuals who carry cancer-predisposing mutations is unknown. Based on observational studies, colonoscopy every 1 to 3 years starting at age 25 years is recommended for individuals known to have HNPCC-associated mutations. Endometrial cancer screening is also recommended, based on expert opinion concerning presumptive benefit. No recommendation is made for or against prophylactic surgery (ie, colectomy, hysterectomy); these surgeries are an option for mutation carriers, but evidence of benefit is lacking. It is recommended that individuals considering genetic testing be counseled regarding the unknown efficacy of measures to reduce risk and that care for individuals with cancer-predisposing mutations be provided whenever possible within the context of research protocols designed to evaluate clinical outcomes.

Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. Cancer Genetics Studies Consortium.

OBJECTIVE: To provide recommendations for cancer surveillance and risk reduction for individuals carrying mutations in the BRCA1 or BRCA2 genes. PARTICIPANTS: A task force with expertise in medical genetics, oncology, primary care, gastroenterology, and epidemiology convened by the Cancer Genetics Studies Consortium (CGSC), organized by National Human Genome Research Institute (previously the National Center for Human Genome Research). EVIDENCE: Studies evaluating cancer risk, surveillance, and risk reduction in individuals genetically susceptible to breast and ovarian cancer were identified using MEDLINE (National Library of Medicine) and from bibliographies of articles thus identified. Indexing terms used were "genetics" in combination with "breast cancer," "ovarian cancer," and "screening," or "surveillance" in combination with "cancer family" and "BRCA1" and "BRCA2." For studies evaluating specific interventions, quality of evidence was assessed using criteria of the US Preventive Services Task Force. CONSENSUS PROCESS: The task force developed recommendations through discussions over a 14-month period. CONCLUSIONS: Efficacy of cancer surveillance or other measures to reduce risk in individuals who carry cancer-predisposing mutations is unknown. Based on expert opinion concerning presumptive benefit, early breast cancer and ovarian cancer screening are recommended for individuals with BRCA1 mutations and early breast cancer screening for those with BRCA2 mutations. No recommendation is made for or against prophylactic surgery (eg, mastectomy, oophorectomy); these surgeries are an option for mutation carriers, but evidence of benefit is lacking, and case reports have documented the occurrence of cancer following prophylactic surgery. It is recommended that individuals considering genetic testing be counseled regarding the unknown efficacy of measures to reduce risk and that care for individuals with cancer-predisposing mutations be provided whenever possible within the context of research protocols designed to evaluate clinical outcomes.

Carcinoid tumors and sarcoidosis--does a link exist?

OBJECTIVE: To attempt to determine whether a relationship exists between carcinoid tumors and sarcoidosis. MATERIAL AND METHODS: We present a series of seven case reports and discuss hypotheses about possible disease associations. RESULTS: Certain malignant lesions have tended to occur in patients with sarcoidosis. Seven patients who were encountered at Mayo Clinic Rochester between 1950 and 1994 had both sarcoidosis and carcinoid tumors. These patients ranged in age from 31 to 66 years, and three of the patients had a history of benign thyroid disorders. Malignant tumors have been thought to be related to sarcoidosis in one of two ways: (1) immunologic abnormalities in sarcoidosis may promote the development of neoplasms or (2) malignant disease may promote the onset of sarcoidosis either by causing local sarcoid reactions that progress or by directly initiating the manifestations of systemic sarcoidosis. Because the chronology of events differed in our seven cases, various mechanisms of action may have a role in the manifestations of these two disease entities. Our cases emphasize the importance of avoiding the diagnosis of disseminated malignant disease in patients with cancer and associated hilar and mediastinal lymphadenopathy without biopsy confirmation of metastatic disease. CONCLUSION: Application of the knowledge gained about the mechanisms of disease in sarcoidosis will perhaps facilitate identification of the pathogenesis of carcinoid tumors and other neuroendocrine tumors.

A multiple prognostic index predictive of disease outcome after irradiation for clinically localized prostate carcinoma.

BACKGROUND: This investigation was conducted to identify independent pretherapy disease-related factors associated with disease outcome in patients with clinically localized carcinoma of the prostate (CaP) and to develop models that incorporated relevant covariates for estimating the risk of disease relapse after irradiation (RT). METHODS: The outcome of 500 patients treated only with RT between March 1987 and June 1993 for clinical Stages T1-4N0,XM0 CaP was evaluated. The risk of disease relapse as a function of individual prognostic variables, and combinations thereof, was determined using logistic regression. RESULTS: With a median follow-up of 43 months (range, 4-103 months), 69 patients (14%) had clinical evidence of local recurrence (27 patients), regional lymph node relapse (4 patients), or metastatic relapse (38 patients) within 5 years of RT. Forty additional patients (8%) had biochemical relapse based solely on the post-RT serum prostate specific antigen (PSA) profile. Clinical tumor stage (P = 0.0006), Gleason score (P = 0.001) of the diagnostic biopsy specimen, and pretherapy PSA (P < 0.0001) were associated with disease relapse. The risk of any relapse within 5 years of RT was determined and graphically displayed as risk estimate plots for combinations of these pretherapy prognostic variables. CONCLUSIONS: The combination of pretherapy clinical tumor (T) stage, Gleason score, and PSA level can be used to obtain improved estimates of the risk for disease relapse in patients treated solely with RT for clinically localized CaP. Risk estimate plots of this type may facilitate exchange of therapeutic outcome information, be instrumental in pretherapy decision-making for the new patient with this condition, and aid in the selection of patients for future studies.

Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer.

PURPOSE: The goal of this study was to determine the efficacy of intensive-course fluorouracil (5FU) plus low-dose leucovorin given for 6 months following potentially curative resection of colon cancer. PATIENTS AND METHODS: Three hundred seventeen patients with high-risk stage II or stage III colon cancer were randomly assigned 3 to 4 weeks following surgery to receive either (1) chemotherapy with six cycles of 5FU (425 mg/m2) plus leucovorin (20 mg/m2) by rapid intravenous injection daily for 5 consecutive days every 4 to 5 weeks, or (2) observation. RESULTS: The median follow-up duration is 72 months for patients still alive. Patients who received postoperative 5FU plus leucovorin experienced significant improvement in time to relapse (P < .01) and survival (P = .02) compared with control patients treated with surgery alone. Stomatitis, diarrhea, and leukopenia were the predominant chemotherapy toxicities. There were no treatment-related deaths. CONCLUSION: These results indicate that intensive-course 5FU plus low-dose leucovorin is effective in preventing tumor relapse and improving survival in patients with high-risk colon cancer. These benefits were seen with only six cycles of treatment, using low-dose leucovorin in combination with 5FU on a schedule convenient for outpatient administration.

Teaching efficacy of a medical education module on genetic testing for cancer.

BACKGROUND: With the identification of the breast cancer susceptibility genes BRCA1 and BRCA2, clinical testing for detection of the mutated genes may be available in the near future. Primary care physicians increasingly serve as full-service providers and gatekeepers and must be aware of presymptomatic testing in order to counsel their patients appropriately. To address this educational need, a new module was incorporated into the genetics course taken by first-year medical students at the Medical College of Virginia. METHODS: The module used small groups, led by genetics faculty and members of the Virginia Breast Cancer Foundation, for discussion of case examples. The medical students' knowledge of and attitudes toward cancer and predictive genetic testing were assessed by a pretest and a posttest. RESULTS: After the module, knowledge scores increased by 27%, and significant changes were seen in the students' attitudes toward issues such as the regulation of testing availability and the psychological effect of testing. Most students consistently felt that predictive genetic testing is beneficial, that they would have the testing themselves, that genetic counseling should be required for testing, and that insurers' access to genetic testing results should be limited. Overall, the module was received favorably by all participants. CONCLUSIONS: Small-group discussion of relevant case examples increases knowledge and awareness of issues regarding presymptomatic genetic testing for breast cancer.