Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer.

BACKGROUND: The value of nephrectomy in metastatic renal-cell cancer has long been debated. Several nonrandomized studies suggest a higher rate of response to systemic therapy and longer survival in patients who have undergone nephrectomy. METHODS: We randomly assigned patients with metastatic renal-cell cancer who were acceptable candidates for nephrectomy to undergo radical nephrectomy followed by therapy with interferon alfa-2b or to receive interferon alfa-2b therapy alone. The primary end point was survival, and the secondary end point was a response of the tumor to treatment. RESULTS: The median survival of 120 eligible patients assigned to surgery followed by interferon was 11.1 months, and among the 121 eligible patients assigned to interferon alone it was 8.1 months (P=0.05). The difference in median survival between the two groups was independent of performance status, metastatic site, and the presence or absence of a measurable metastatic lesion. CONCLUSIONS: Nephrectomy followed by interferon therapy results in longer survival among patients with metastatic renal-cell cancer than does interferon therapy alone.

Characterization of a newly established human pancreatic carcinoma cell line, UK Pan-1.

BACKGROUND: A highly tumorigenic cell line designated as UK Pan-1 was established in a surgically removed human pancreatic adenocarcinoma and characterized as having many of the genotypic and phenotypic alterations commonly found in pancreatic tumors. METHODS: The cell line was characterized by its morphology, growth rate in monolayer culture and soft agar, tumorigenicity in nude mice, and chromosomal analysis. Furthermore, the status of p53, Ki-ras mutation and transforming growth factor (TGF)-/receptor expression were determined. The characteristics of UK Pan-1 were compared with those of other commonly used pancreatic carcinoma cell lines. RESULTS: Quiescent UK Pan-1 cells could be stimulated to proliferate in growth factor free nutrient media, indicating a growth factor independent phenotype. UK Pan- 1 cells grew in soft agar and rapidly formed tumors in nude mice. This cell line possesses a mutation at codon 12 of the c-Ki-ras-2 gene that is commonly found in pancreatic carcinoma. Fluorescence in situ hybridization showed that two alleles of p53 tumor suppressor gene were present in UK Pan-1. However, sequencing analysis revealed a mutation in one allele at exon 8, codon 273 (G to A; Arg to His). Additional growth assays indicated that the cell line was insensitive to negative growth regulation induced by exogenous TGF-beta. Molecular analysis of the TGF-beta signaling pathway showed that UK Pan-1 did not express appreciable levels of the TGF-beta receptor type I, II, or III mRNAs, but did express DPC4 mRNA. Karyotype analysis revealed an 18q21 deletion indicating a possible loss of heterozygosity for DPC4, as well as other chromosomal deletions and rearrangements. CONCLUSIONS: This study indicates that UK Pan-1 is a highly tumorigenic cell line possessing a molecularly complex pattern of mutations that may be used as a model to further the understanding of the mechanisms responsible for the development of pancreatic carcinoma.

A multidimensional approach to breast cancer education.

BACKGROUND: This study was undertaken to present a multidimensional breast cancer education package (BCEP) to medical students in an effort to improve breast cancer education. METHODS: The students were exposed to a four-part BCEP consisting of a hands-on structured clinical instruction module (SCIM), a lecture, a problem-based learning (PBL) small-group discussion, and a written manual. Each component was evaluated with a questionnaire. Students responded to the items using a five-point Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree). RESULTS: The mean overall evaluations for the BCEP components were: SCIM, 4.6; lecture, 4.0; manual 3.8, and PBL discussion, 3.6. Highly rated qualities of the SCIM included organization (4.7), faculty preparedness (4.8), and opportunity to practice skills (4.5). The students agreed that the lecture (4.1), manual (3.8), and PBL discussion (4.2) had prepared them for the SCIM. CONCLUSION: This innovative BCEP effectively improved students' understanding of breast cancer.

Preoperative chemoradiation in fixed distal rectal cancer: dose time factors for pathological complete response.

PURPOSE: Preoperative chemoradiation is being utilized extensively in the treatment of rectal cancer. However, a variety of dose time factors in both delivery of chemotherapy and irradiation remain to be established. This study was undertaken to examine the impact of dose time factors on pathological complete response (pCR) rates following preoperative chemoradiation for fixed rectal cancer. METHODS AND MATERIALS: Thirty-three patients with fixed rectal cancers were treated with combined 5-fluorouracil (5-FU) chemotherapy and pelvic radiation. Twenty-one patients received bolus 5-FU during the first 3-5 days of radiation and repeated on days 28-33 of their radiation treatment. Twelve patients were treated with continuous infusion (CI) 5-FU, 225 mg/m(2) for the duration of the pelvic radiation. Fifteen patients received a planned total radiation dose of 45 to 50 Gy and 18 patients received a dose of 55 to 60 Gy. Surgical resection was then carried out 6-8 weeks after completion of treatment. RESULTS: Diarrhea was the most frequent acute toxicity. Grade 3 diarrhea was observed in 6 patients requiring treatment interruption and was not related to the chemotherapy regimen. There was no Grade 4 or 5 toxicity. pCR was observed in 2 of 21 (10%) patients treated with bolus 5-FU as compared to 8 of 12 (67%) for patients treated with CI (p = 0.002). pCR were observed in 8 of 18 (44%) patients receiving radiation dose > or = 5500 cGy as compared to 2 of 15 (13%) patients treated to a dose < or = 5000 cGy (p = 0.05). In the high-dose radiation (> or = 5500 cGy) group, a significant difference in pCR rate was observed in patients treated with CI, 8 of 12 (67%) (p = 0.017) as compared with bolus 5-FU (0 of 6). There was no significant difference in operative morbidity or in wound healing between patients treated with bolus 5-FU or CI or within the groups treated with low or high doses of radiation. Three patients have developed local recurrence at 14 and 24 months, two in the low-dose group treated with bolus 5-FU and one patient in the CVI group. The overall 5-year survival for the whole group is 71%. CONCLUSION: Dose intensity of 5-FU and dose of radiation correlate significantly with the likelihood of achieving a pCR. Continuous infusion 5-FU (CI) and a preoperative radiation dose of 5500 cGy or higher can achieve pCR rates of approximately 50%, even in fixed cancers of the rectum.

Stability and change in posttraumatic stress disorder symptoms following breast cancer treatment: a 1-year follow-up.

While some recent research has examined the prevalence and severity of posttraumatic stress disorder (PTSD)-like symptoms following cancer treatment, no research has examined temporal change or stability in these symptoms in cancer survivors. Female breast cancer survivors (n=46) participated in an initial telephone interview and a follow-up interview 12 months later. PTSD symptoms associated with breast cancer were assessed using the PTSD Checklist-Civilian version (PCLC). In general, PTSD symptoms in this population did not diminish over time. While group analyses indicated that PCLC-total and subscale scores were stable across the two assessments, analyses of PCLC scores indicated that many patients exhibited fairly large (>0.5 S.D.) increases and/or decreases in PCLC-total or subscale scores. Some evidence suggested that decreases in PCLC scores between the two study assessments were associated with greater social support and experience of fewer traumatic stressors prior to breast cancer diagnosis. Most significantly, the research suggested that women with greater PTSD symptoms at the initial interview were less likely to participate in the follow-up interview. Implications of this for research and clinical management of PTSD in this population are discussed.

Rheumatoid symptoms following breast cancer treatment: a controlled comparison.

The prevalence of rheumatoid symptoms following breast cancer (BC) treatment was examined. Breast cancer patients (n = 111) who were a mean of 27.6 months postcompletion of BC treatment and 99 otherwise healthy women with benign breast problems (BBP) completed a self-report measure that assessed current joint pain, swelling, and stiffness, as well as measures of quality of life. Results supported a hypothesized link between BC and rheumatoid symptoms: (1) the BC group was more likely to report joint stiffness lasting more than 60 min following morning waking; (2) the prevalence of unilateral or bilateral joint point or swelling was greater (P < 0.10) in the BC group for four of 10 joint-symptom combinations examined, with differences between the BC and BBP groups in upper extremity joint swelling particularly pronounced; and (3) 41% of the BC group reported that current rheumatoid symptoms exceeded those experienced prior to diagnosis. Within the BC group, the data did not support postchemotherapy rheumatism as an explanation for rheumatoid symptoms. Rather, data suggested that symptoms were associated with surgical management of BC. Finally, among women in the BC group with the most severe joint pain, only a minority were receiving medication for these symptoms. Given the relationship between rheumatoid symptoms and quality of life, more systematic research examining potential contributing factors such as menopausal status, concurrent lymphedema, and weight gain is warranted.

Advances in the pathogenesis and treatment of thyroid cancer.

Thyroidectomy remains the mainstay of treatment for thyroid carcinoma. The extent of surgical resection, however, remains controversial as most patients will have excellent long-term prognosis and because some of the standard staging and prognostic information are not available at the time of surgical resection. The different staging and risk group definitions for thyroid carcinoma are not superior to the Tumor-Node-Metastasis classification of the American Joint Commission in Cancer (AJCC), which is universally available and accepted and should be used to report treatment outcomes. Recent advances in the molecular pathogenesis of thyroid malignancy will help identify high-risk patients who would benefit from aggressive surgical resection and adjuvant treatment.

Physical symptoms, distress, and breast cancer risk perceptions in women with benign breast problems.

Physical symptoms, general and breast cancer-specific distress, and perceived breast cancer risk were assessed in 66 women with benign breast problems (BBP) and 66 age-matched healthy comparison (HC) women. BBP women reported significantly greater worry about breast cancer than HC women. Breast symptom incidence and breast cancer risk perceptions were found to mediate group differences in breast cancer worry. Hierarchical regression analyses indicated that perceptions of control over a potential breast cancer prognosis moderate the impact of breast symptoms on reports of breast cancer worry. Implications for risk counseling with BBP women are discussed.

Thyroid lymphoma: is there a role for surgery?

The role of surgery in the treatment of Stage I and II non-Hodgkin's thyroid lymphoma (NHTL) is not well defined. At our institution, we have treated seven patients (six women and one man) with NHTL during the past 6 years. Three patients (43%) had a prior history of thyroid disease, usually lymphocytic thyroiditis. Clinical symptoms included a rapidly enlarging neck mass (86%), dysphagia (71%), dyspnea (71%), and hoarseness (71%). Five patients (71%) had hypothyroidism; one patient, hyperthyroidism; and one patient, normal thyroid function. Five patients underwent fine-needle aspiration (FNA) at our institution. In three instances, FNA results were indicative of NHTL; the remaining FNA tests yielded no diagnosis. Surgical procedures were varied: incisional biopsy (n = 4), limited tumor debulking with tracheostomy (n = 2), and thyroidectomy (n = 1). Each of the seven patients was found to have large cell lymphoma. Treatment consisted of combination chemotherapy with consolidative irradiation. All tumors dramatically decreased in size soon after the initiation of therapy. One patient refused radiotherapy. All patients except one are still alive (median follow-up, 24 months). In conclusion, 1) a diagnosis of NHTL, although rare, should be considered when patients have rapidly growing goiters; 2) FNA is a useful first step in diagnosing NHTL; 3) NHTL is exquisitely sensitive to both chemotherapy and radiation; 4) surgical intervention is generally confined to incisional biopsy with occasional limited pretracheal tumor debulking; and 5) when a biopsy is obtained from a patient suspected of having NHTL, immediate processing by the pathologist is recommended so that material can be obtained for special studies as needed.

Advances in the diagnosis and therapy of adrenal tumors.

There continues to be controversy regarding the optimal evaluation and treatment of adrenal tumors. Magnetic resonance imaging, metaiodobenzylguanidine scan, single-photon emission tomography imaging, endoscopic ultrasound, and radiolabeled somatostatin analogues are just a few of the newer imaging techniques being investigated to improve our ability to obtain a specific diagnosis of an adrenal mass. Although the diagnosis and treatment of pheochromocytomas are relatively straightforward, the evaluation and treatment of incidentally discovered adrenal masses is less clear-cut. The management of an incidentaloma is guided by two principle considerations: whether the tumor has hormonal activity, and its malignant potential. In addition to diagnostic advances, refinements continue to be made regarding surgical management of these lesions. Laparoscopic adrenalectomy is fast becoming the procedure of choice for benign-appearing adrenal masses with appropriate indications for operative removal.

Postmastectomy/postlumpectomy pain in breast cancer survivors.

Few studies have focused on careful assessment of postmastectomy pain (PMP); a chronic neuropathic pain syndrome that can affect women postlumpectomy or postmastectomy for breast cancer (BC). Study aims were to determine the prevalence of PMP in an outpatient sample of breast cancer survivors (BCS), describe subjective and objective characteristics of PMP, and examine the relationship between PMP and quality of life. Breast cancer survivors (n = 134) participated in telephone interviews, and those reporting PMP (n = 36) were invited to a pain center for further evaluation and treatment. Results show PMP is a distinct, chronic, pain syndrome affecting 27% of BCS. Findings support the need for clinical trials evaluating the effectiveness of nonpharmacological or cognitive behavioral therapies in alleviating mild to moderate PMP.

The structured clinical instruction module as a tool for improving students' understanding of breast cancer.

The Structured Clinical Instruction Module (SCIM) is a novel format for teaching clinical skills. A multidisciplinary SCIM was presented to 30 medical students to improve their understanding of breast cancer. The SCIM consisted of 12 10-minute stations, each covering a different aspect of the diagnosis and management of breast cancer (e.g., history, physical examination, treatment options, mammography, cytology, and pathology). The students rotated through the various stations in groups of three. Nine patients and 14 faculty members participated. At the end of the SCIM, students, faculty, and patients rated their level of agreement (on a five-point scale ranging from "Strongly Disagree" to "Strongly Agree") with statements on a multi-item evaluation questionnaire. All ratings were positive. The students agreed most that the small-group format was an effective instructional method (mean, 4.6). Both students and faculty agreed that the SCIM increased students' clinical skills (mean, 4.4 in both evaluations). Faculty expressed a willingness to participate in future such workshops (mean, 4.6). Patients agreed most strongly that they enjoyed the SCIM (mean, 5.0) and that faculty feedback to students was excellent (mean, 5.0). The SCIM was well received by all participants in this pilot project.

The multidisciplinary structured clinical instruction module as a vehicle for cancer education.

BACKGROUND: The Structured Clinical Instruction Module (SCIM) modifies the Objective Structured Clinical Examination (OSCE) for teaching purposes. This study determined the effectiveness of a breast cancer SCIM in enhancing residents' clinical skills. METHODS: Twenty-five residents, 15 faculty members, and 12 breast cancer patients (simulated and actual) participated in the multistation, multidisciplinary SCIM. Afterward, faculty members, residents, and patients evaluated the SCIM. Residents completed an 18-item self-assessment of their skills before and after the SCIM. RESULTS: All residents, faculty members, and patients rated the SCIM as either outstanding or above average as an educational experience. The residents' self-assessments of their skills were significantly higher after the SCIM than before. CONCLUSIONS: This study shows that residents are aware of their deficiencies in breast cancer management. The SCIM provides an excellent format for residents to improve their clinical skills.

Measuring the ability of residents to manage oncologic problems.

BACKGROUND: An OSCE was used to measure the ability of a cohort of residents to manage oncologic problems. METHODS: Nine oncologic clinical problems were presented to 56 surgical residents. Each problem contained a 5-minute data-gathering period (DGP) and a 5-minute data-interpretation period (DIP). A performance score was determined for each resident for each problem. Reliability was estimated by coefficient alpha; validity, by the construct of experience. Wilks's lambda criterion was used to determine whether training level could be identified by OSCE performance. RESULTS: The DGP reliability was 0.80; the DIP, 0.49. Senior residents performed significantly better than junior residents (P = 0.0001), who performed significantly better than interns (P = 0.0009). Of the residents, 62% were competent on the DGP, but only 21% on the DIP. Important deficits in knowledge and clinical skills were apparent at all levels of training. CONCLUSION: The education and evaluation of residents in oncology need improvement.

Diagnosis and management of pheochromocytoma.

Pheochromocytomas are rare endocrine tumors. They can be associated with a wide variety of symptoms, although hypertension is the most consistent clinical sign. Ultrasonography is very effective in localizing these tumors, but extra-adrenal pheochromocytomas are best diagnosed with 131I-metaiodobenzylguanidine scanning. Extensive investigation is ongoing to determine markers for the presence of these tumors and diagnostic tests that localize the site of pheochromocytomas, with extensive research at the molecular level. New surgical techniques are being employed, particularly laparoscopic adrenalectomy. Finally, complications of pheochromocytomas are discussed in several papers; the primary concern is cardiac problems.

Efficacy of p120 antisense-mediated therapy for pancreatic cancer.

p120 antisense oligodeoxynucleotides were used to determine whether they inhibited cell growth of MIA PaCa-2, a highly tumorigenic human pancreatic carcinoma cell line. Growth inhibition assays were determined in vitro by the ability of these oligomers to inhibit DNA synthesis and cell growth. For in vivo studies, nude mice were injected with cells and palpable tumors were found in 16 of 20 animals by day 14. Sixteen animals (8 in each group) were then treated daily (25 mg/kg intraperitoneally) for up to 40 days with nonsense control oligomers or p120 antisense oligomers. p120 Antisense oligomers inhibited the in vitro proliferation of MIA PaCa-2 cells in a dose-dependent manner, and optimal growth inhibition of greater than 90% was achieved at an antisense oligomer concentration of 100 micromol/L. The tumor volume was calculated for antisense- and nonsense-treated animals. Fifteen days after the beginning of treatment, control animals had a significantly greater (P=0.0035) tumor volume (425=244 mm3 above baseline) as compared to p120 antisense-treated animals (166+/-116 mm3). Seven of the eight control animals formed tumors that had a volume greater than 1200 mm3 45 days after treatment was begun, whereas only three of eight p120 antisense-treated animals had tumors that were this large. Two of the latter three animals had relatively large, palpable tumors (>150 mm3) prior to treatment. Twenty days after treatment was stopped (day 60), all animals had tumors larger than 1200 mm3. p120 Antisense oligomers were effective for inhibiting in vitro growth of the pancreatic cancer cell line MIA PaCa-2. In preliminary studies, p120 antisense oligomers appeared to inhibit the rate of growth in nude mice; however, no cures were achieved. The most effective response was seen in animals with initial low tumor burden.

Giant adrenal myelolipoma.

Adrenal myelolipomas are nonfunctioning benign tumors composed of hematopoietic elements and mature adipose tissue. These tumors usually remain small and asymptomatic; occasionally, however, they reach massive proportions and become symptomatic. To date, only two giant adrenal myelolipomas (>4,000 g) have been described in the literature. We describe the diagnostic evaluation and the operative management of the third largest adrenal myelolipoma reported.

Psychosocial adjustment and quality of life in women with breast cancer and benign breast problems: a controlled comparison.

Comparison of psychosocial adjustment in women with breast cancer (BC) and women with benign breast problems (BBP) has been hampered by a failure to control for age differences between these groups, as well as a failure to assess positive psychosocial adaptation in addition to psychological distress. Age-matched women with breast cancer (n = 80) and benign breast problems (n = 80) completed measures of psychological distress, positive psychosocial adaptation, and general quality of life (QOL). Breast cancer patients had completed primary treatment for breast cancer a mean of 24.6 months prior to participation (range, 6-57 months). Comparison of the BC and BBP groups indicated that the BC group reported (1) poorer physical health and functioning, (2) no differences in psychological distress, and (3) greater positive psychosocial adaptation, such as improved life outlook, enhanced interpersonal relationships, and deeper spiritual and religious satisfaction. Results support the theoretical position that cancer is a transitional event, that is, a traumatic event that alters an individual's assumptive world with the potential to produce long-lasting changes of both a positive as well as negative nature. This underscores the importance of using measures of both psychological distress and positive psychosocial adaptation when assessing psychological adjustment following transitional events such as breast cancer.

Marjolin's ulcer of the foot caused by nonburn trauma.

Marjolin's ulcers are malignancies that arise from previously traumatized, chronically inflamed, or scarred skin. We report a case of squamous cell carcinoma arising in a foot wound 42 years after the time of injury. The historical background, epidemiology, pathophysiology, diagnosis, treatment, and prognosis of Marjolin's ulcer are reviewed. Diagnosis is best accomplished by punch biopsy or excision of suggestive lesions. Wide local excision is required and amputation may be necessary to achieve an adequate margin. Regional lymph node dissection should be done if regional nodes are palpable. Elective lymph node dissection is controversial but should be considered if the tumor is poorly differentiated. Lymph node metastases and high tumor grade indicate a poor prognosis. Clinicians should be diligent in the long-term surveillance of all significant scars or areas of chronic inflammation.

Surgical management of pancreatic carcinoma.

Since 1935, when Whipple originally described the removal of periampullary tumors, both the surgical method and the outcome associated with it have changed extensively. The mortality rates associated with the procedure as performed today have decreased from 20% to less than 5%; the 5-year survival rate after resection of pancreatic cancer has increased from 3.5% to more than 20% in some studies. These improvements are the result of improved perioperative care and the numerous modifications and technical refinements to the procedure itself. The most important determinants of long-term survival, however, relate to the biology of the tumor. Unfortunately, most pancreatic cancers are diagnosed at an advanced stage and are often unresectable. In this setting, any surgical intervention will be purely palliative in nature. Such procedures can reduce the symptoms associated with the disease and can slightly extend survival times. Several nonoperative approaches can also offer significant palliation to patients with inoperable pancreatic cancer.