The search for level I evidence in solid-tumor oncology.

BACKGROUND: We have developed a method to identify, filter, review, and distribute the published level I evidence for solid tumor oncology. METHODS: A standardized MEDLINE search identified prospective randomized controlled trials (PRCTs) in solid tumor oncology. Only PRCTs with therapeutic end points were included. All references were reviewed by a surgical oncology fellow in consultation with experts in the field. The full citations were imported into a comprehensive database. Data on statistical methods according to the Consolidated Standard of Reporting Trials statement were tabulated along with reviewer's comments. A designation of Ia was given to articles that were well designed and significant contributions to their field. The database powers a dynamic, easily searchable Web site on our intranet and is available in personal digital assistant (PDA) format. RESULTS: By using standard search criteria, only .03% of the 11 million articles listed in MEDLINE are PRCTs concerning therapy for solid organ malignancies. Approximately 14% of reviewed articles were given a designation of Ia. Having comprehensive data readily available with intranet access or PDAs during conferences enhances their educational value and specificity. CONCLUSIONS: We have developed an exciting tool that uses a highly trained filter to screen and record the medical data available to the clinician. This information has been made available and portable by using the Internet and PDAs.

Amputation for recurrent soft tissue sarcoma of the extremity: indications and outcome.

BACKGROUND: Limb salvage after primary site failure of extremity soft tissue sarcoma is a challenging problem. Amputation may be the most effective treatment option in selected patients with local recurrence. We compared the outcome of patients treated with amputation versus limb-sparing surgery (LSS) for locally recurrent extremity sarcoma. METHODS: From 1982 to 2000, 1178 patients with localized primary extremity sarcoma underwent LSS. Of these, 204 (17%) developed local recurrence. Eighteen (9%) required major amputation and the remainder underwent LSS, of which 34 were selected for matched-pair analysis according to established prognostic variables. Rates of recurrence or death were estimated by the Kaplan-Meier method. Following adjustment for prognostic variables, a Mantel-Haenszel test was used to compare the outcome between the two treatment groups. RESULTS: Patients in each group were well matched. All patients had high-grade tumors deep to the fascia. Median time to local recurrence was similar for both groups. Median follow-up was 95 months. Amputation was associated with a significant improvement in local control of disease (94% vs. 74%; P = .04). We observed no difference in disease-free (P = .48), disease-specific (P = .74), or overall survival (P = .93) between the two groups. Median postrecurrence survival was 20 months and 5-year OS was 36% for the entire study group. CONCLUSIONS: Limb-sparing treatment achieves local control in the majority of recurrent extremity sarcomas for which amputation is infrequently indicated. Amputation improves local disease control but not survival under these circumstances.

Staging work-up and post-treatment surveillance of patients with melanoma.

Strategies based on evidence are required to accurately stage and effectively follow patients with melanoma. The goal of staging is to define the extent of disease at the time of presentation to direct and assign prognosis. Patient surveillance is performed to assess treatment results and detect recurrences amenable to further treatment. Staging and surveillance require careful use of resources to be cost effective. This article addresses preoperative staging and post-treatment surveillance of patients with melanoma and outlines a method of follow-up based on available data.

Sentinel lymph node biopsy for breast cancer: the role of previous biopsy on patient eligibility.

Several reports have demonstrated the accurate prediction of axillary nodal status with radiolocalization and selective resection of sentinel lymph nodes (SLNs) in patients with breast cancer (BC). Because of concerns over lymphatic disruption, several authors have proposed that prior excisional breast biopsy is a contraindication for SLN biopsy. Clear unfiltered 99mtechnetium-sulfur colloid (1.0 mCi) was injected around the perimeter of the breast lesion (palpable and nonpalpable) or prior biopsy site. Resection of the radiolocalized SLN was then performed. Axillary lymph node dissection was performed immediately after SLN biopsy in the first 57 patients. Eighty-two BC patients underwent SLN biopsy. The SLN was localized in 98 per cent (80 of 82). The type of previously performed diagnostic biopsy or the location of the primary lesion did not influence the ability to localize the sentinel lymph node. In the 57 patients who had axillary lymph node dissection, metastatic disease was identified in 23 per cent (13 of 57). Axillary nodal status was accurately predicted in 98 per cent (56 of 57). Early experience with radiolocalization and selective resection of SLN in BC remains promising. By demonstrating the effective localization of the SLN regardless of the extent of prior biopsy, these data support expanding the number of patients potentially eligible for SLN biopsy.

Decision making on surgical palliation based on patient outcome data.

BACKGROUND: Strategies for the effective application of palliative procedures are infrequently standardized and incompletely understood. The effect on patient outcome as determined by elements such as resolution of chief complaints, quality of life, pain control, morbidity of therapy, and resource utilization should predominate decisions regarding surgical palliative care. METHODS: Articles published between 1990 and 1996 on the surgical palliation of cancer were identified by a MEDLINE search and reviewed for designated parameters considered important for good palliative care. RESULTS: A total of 348 citations were included. Entries considered these fundamental elements: cost (2%); pain control (12%); quality of life (17%); need to repeat the intervention (59%); morbidity and mortality (61 %); survival (64%); and physiologic response (69%). Established methods for quality of life and pain assessment were sporadically utilized. CONCLUSIONS: In the current surgical literature, there is uncommon reporting of the range of data required to recommend sound palliative surgical choices.

Guidelines for the safe use of radioactive materials during localization and resection of the sentinel lymph node.

BACKGROUND: Several reports have demonstrated accurate prediction of nodal metastasis with radiolocalization and selective resection of the radiolocalized sentinel lymph node (SLN) in patients with breast cancer and melanoma. As reliance on this technique grows, its use by those without experience in radiation safety will increase. METHODS: Tissue obtained during radioguided SLN biopsies was examined for residual radioactivity. Specimens with a specific activity greater than the radiologic control level (RCL) of 0.002 microCi/g were considered radioactive. Radiation exposure to the surgical team was measured. RESULTS: A total of 24 primary tissue specimens and 318 lymph nodes were obtained during 57 operations (37 for breast cancer, 20 for melanoma). All 24 (100%) of the specimens injected with radiopharmaceutical and 89 of 98 (91%) of the localized nodes were radioactive after surgery. Activity fell below the RCL 71+/-3.6 hours in primary tissue specimens, 46+/-1.7 hours in nodes from melanoma patients, and 33+/-3.5 hours in nodes from breast cancer patients (P = .037). The hands of the surgical team (n = 22 cases) were exposed to 9.4+/-3.6 mrem/case. CONCLUSION: Although low levels of radiation exposure are associated with radiolocalization and resection of the SLN, the presented guidelines ensure conformity to existing regulations and allow timely pathologic analysis.

Diagnosis and management of the autonomously functioning thyroid nodule: the Walter Reed Army Medical Center experience, 1975-1996.

In order to characterize the clinical and laboratory features of autonomously functioning thyroid nodules (AFTNs), and to assess optimal diagnosis and management of patients with this disorder, we performed a retrospective analysis of 49 such patients over a 22-year period encompassing January 1975 to November 1996. The following data were analyzed: thyroid hormone levels, thyroid scintiscan, radioiodine uptake, fine-needle aspiration biopsy, triiodothyronine (T3) suppression testing, thyrotropin-releasing hormone (TRH) stimulation test, and thyroid ultrasound. Clinical outcomes assessed included persistent hyperthyroidism, hypothyroidism, and nodule shrinkage after treatment, or in patients followed without definitive therapy, nodule growth, spontaneous degeneration, and progression to hyperthyroidism. Biochemical hyperthyroidism, often subclinical, was found in 73.5% of patients at presentation and in an additional 24.4% of patients during subsequent follow-up. The introduction of sensitive thyrotropin (TSH) testing during the period of study resulted in a decrease in the use of the T3-suppression test and TRH stimulation test from 100% and 20%, respectively, in the period from 1976-1980, to 4% each in the period from 1991-1996. T3-thyrotoxicosis occurred in 12.2% of patients. Thyrotoxicosis at any time during the course of follow-up was positively correlated with nodule size at diagnosis. Definitive therapy, used in 42.8% of patients, consisted of radioiodine ablation (38.1%) or thyroidectomy (61.9%). No patient had recurrence of thyrotoxicosis after definitive therapy, but 25% became hypothyroid. During follow-up for a mean of 30.9 months, nodules enlarged in 25% of patients overall, or 33% of patients not receiving definitive therapy. Cystic degeneration was documented in 26.5% of patients, although this change rarely reversed subclinical hyperthyroidism. The diagnosis of an AFTN requires a demonstration of TSH-independent nodular hyperfunction. The introduction of sensitive TSH assays has simplified the evaluation of AFTN patients and revealed a high prevalence of subclinical thyroid hyperfunction in this disorder. In view of current increased awareness of adverse consequences associated with subclinical hyperthyroidism and the rarity of spontaneous resolution of hyperthyroidism in AFTN patients (despite a propensity for spontaneous hemorrhage), definitive therapy is recommended. Both radioiodine and hemithyroidectomy have high cure rates and a low posttreatment incidence of hypothyroidism.

Contributions from surgeons to clinical trials and research on the management of soft tissue sarcoma.

BACKGROUND: Surgical resection is the primary treatment for soft tissue sarcoma. Surgeons are in a position to develop and define appropriate treatment strategies for this disease. In an effort to define the contributions of surgeons to the management of sarcoma, the surgical and clinical oncology literature from January 1983 through June 1996 was reviewed. METHODS: A computerized literature search of the Cancerlit database for January 1983 to June 1996 was performed. The search was limited to the topic of soft tissue sarcoma and was further confined to 15 journals that publish articles relevant to surgical management. These studies were then categorized by multiple parameters and analyzed. RESULTS: The Cancerlit file contained 4478 articles in which sarcoma was the primary topic. When the search was limited to 15 journals frequently read by surgeons, 479 references (11%) were retrieved. Within the surgical literature, 95 of the 479 articles (20%) described prospective studies, of which 33 were prospective and randomized. These studies represent all but three of the prospective randomized trials within the literature during the time period reviewed. The management of patients with sarcoma was evaluated in 26 of the prospective randomized trials; of these, 13 trials evaluated adjuvant chemotherapy, three evaluated adjuvant radiotherapy, and ten evaluated the chemotherapeutic treatment of metastatic disease. Surgical oncologists were the first or senior author on 10 of the 16 prospective randomized studies regarding adjuvant radiation or chemotherapy. Four of the 16 trials evaluating adjuvant therapy contained more than 100 patients, and three of those four were from cooperative group efforts. All but one of the studies of adjuvant therapy with less than 100 patients were from single institutional trials. CONCLUSIONS: Although the surgical and clinical oncology literature on soft tissue sarcoma is composed primarily of retrospective reviews, the prospective randomized trials reported represent almost all of the randomized trials in the literature and have significant contributions from surgeons. Surgeons can guide and design clinical trials, but overall patient accrual as represented by soft tissue sarcoma is low, and may be improved through cooperative group efforts.

Ultrasonographically guided injection improves localization of the radiolabeled sentinel lymph node in breast cancer.

BACKGROUND: Several reports have demonstrated the accurate prediction of axillary nodal status (ANS) with radiolocalization and selective resection of sentinel lymph nodes (SLN) in breast cancer. To date, no technique has proven to be superior in localizing the SLN. METHODS: 1.0 mCi of clear unfiltered 99mtechnetium sulfur colloid was injected under ultrasonographic (US) guidance around the perimeter of the breast lesion (palpable and nonpalpable) or previous biopsy site. Resection of the radiolocalized nodes was performed, followed by complete axillary lymph node dissection (AXLND). RESULTS: Forty-two breast cancer patients underwent SLN biopsy after US-guided radiopharmaceutical injection. The SLN was localized in 41 patients (98%). The type of previously performed diagnostic biopsy did not influence the ability to localize the sentinel lymph node. Pathology revealed nodal metastasis in 7 of the 41 evaluable patients (17%). ANS was accurately predicted in 40 of 41 patients (98%). CONCLUSIONS: Early experience with radiolocalization and selective resection of SLN in breast cancer remains promising. Use of US-guided injection facilitates localization of the SLN, perhaps as a result of more accurate placement of the radionuclide marker. Use of this technique allowed for effective management of patients regardless of tumor size or the extent of prior biopsy, thereby expanding the potential number of eligible patients for SLN biopsy.

Appendectomy: a contemporary appraisal.

OBJECTIVE: The authors present an accurate and comprehensive snapshot of appendicitis and the practice of appendectomy in the 1990s. METHODS: Appendectomies were performed on 4950 patients in 147 Department of Defense hospitals worldwide over a 12-month period ending January 31, 1993. RESULTS: The median age was 23 years (range, 6 months to 82 years) with 64% males and 36% females. The patients were assigned a diagnosis of normal appendix in 632 (13%) cases, acute appendicitis in 3286 (66%) cases, and perforated appendicitis in 1032 (21%) cases. There were no differences in perforation and normal appendix rates between those operations performed in teaching hospitals versus community hospitals or between high-volume hospitals (> or = 100 appendectomies/year) versus low-volume hospitals. Both a preoperative temperature > or = 100.5 and a preoperative leukocyte count > or = 10,000 were incapable of discriminating between patients with appendicitis and those with a normal appendix. Multivariate analysis showed a significantly increased risk of perforation associated with age younger than or equal to 8 years (38% vs. 18%) and age older than or equal to 45 years (49% vs. 18%). Females had a significantly higher rate of normal appendices (19% vs. 9%) and a lower rate of perforation (18% vs. 23%). The complication rates to include reoperation and intraabdominal sepsis were markedly increased in those patients with perforation. There were four deaths in this series (0.08%). CONCLUSIONS: Despite a marked decline in associated mortality over the past 50 years, rates of perforation and negative appendectomy remain unchanged because they are influenced strongly by factors untouched by the intervening technologic advances.

Appendectomy. Improving care through quality improvement.

OBJECTIVE: To evaluate the practice of appendectomy in Department of Defense hospitals worldwide in a large-scale quality improvement initiative. DESIGN: Case series study. POPULATION AND SETTING: A total of 4950 consecutive nonincidental appendectomies performed in 147 Department of Defense hospitals worldwide during a 12-month period ending January 31, 1993. RESULTS: The mean age was 25.5 years, with 64% males and 36% females. The patients were assigned a diagnosis of normal appendix (negative appendectomy) in 632 cases (12.8%), acute appendicitis in 3286 cases (66.4%), and perforative appendicitis in 1032 cases (20.9%). The influence of inpatient and outpatient delays on perforation and negative appendectomy rates were studied. In at least 52% of all patients ultimately assigned a diagnosis of perforative appendicitis, the perforation occurred before the first outpatient contact with the health care system, and in at least 68% of all patients ultimately assigned the diagnosis of perforative appendicitis, the perforation occurred before surgical evaluation and admission. Neither outpatient delay in diagnosis nor inpatient delay in diagnosis and treatment was associated with a significant change in the rate of negative appendectomy. CONCLUSIONS: Perforation rates are determined predominantly by patient- and primary care-related factors over which surgeons have little control. Negative appendectomies are predominantly related to the wide overlap in presenting signs and symptoms between appendicitis and the diseases that most often mimic it but do not require operative intervention. Whereas studies of this type are useful for identifying potential problems at the health care system level, the relatively small number of appendectomies performed by each surgeon precludes analysis at the practitioner level.

Death and dollars: the cost of dying in the surgical intensive care unit.

INTRODUCTION: The effect of resuscitation status on the use of laboratory and radiologic studies was analyzed in patients at the Walter Reed Army Medical Center's Surgical Intensive Care Unit. METHODS: A retrospective assessment of laboratory and radiologic charges incurred during the last 48 hours of life by 81 patients who died in the Surgical Intensive Care Unit between 1990 and 1992 was performed. Data were analyzed after separation by patient's resuscitation status. Each patient was assigned a resuscitation category: no limitation, do not resuscitate (no CPR in event of arrest), or limited therapy (specific order limiting care or monitoring). RESULTS: There were 4,095 laboratory tests performed for a total charge of $191,247. Arterial blood gas testing accounted for over $75,000 of these charges. Resuscitation status significantly affected test frequency. CONCLUSIONS: During the last 48 hours of life in an intensive care unit, the use of laboratory tests and radiologic exams has a substantial effect on the cost of care and is modified by the patient's resuscitation status.

Long-term impact of previous breast biopsy on breast cancer screening modalities.

Approximately 80% of breast biopsies are performed for what proves to be a benign process. The patients who undergo these procedures should continue screening with breast physical examination and mammography. The long-term impact of breast biopsy on these screening modalities has not been well studied. We performed a prospective, follow-up evaluation in 63 patients who underwent needle localization biopsy with benign histology at our institution between 6 and 7 years ago. This evaluation consisted of a directed history, breast physical examination, and follow-up mammogram. Two patients (3%) had undergone mastectomy for an interval breast cancer; 17 others (28%) had undergone subsequent biopsies. No patient had changes on physical examination of the biopsy site. All mammograms were evaluated as normal or as having benign abnormalities. Excisional breast biopsy does not generally produce long-term changes affecting the interpretation of breast physical examination or mammography.

Hepatic metastases from soft-tissue sarcoma.

OBJECTIVE: Hepatic metastases from soft-tissue sarcoma are evaluated to define treatment and its limitations. METHODS: From 981 adult patients with diagnoses of soft-tissue sarcoma, 65 patients with hepatic metastases were studied. RESULTS: An intra-abdominal primary site was present in 61 of 65 patients, with 85% high-grade leiomyosarcoma. Hepatic resection was performed in 14 patients (22%). All patients have had recurrences after hepatic resection-11 of 14 in the liver--with a median survival of 30 months. Chemotherapy resulted in partial response in three patients and no complete responses. Survival is not influenced by grade, type, primary site, disease-free interval, chemotherapy, or hepatic resection. CONCLUSIONS: The uncommon response to conventional chemotherapy does not support its use in the treatment of hepatic metastases from soft-tissue sarcoma. Extent of disease limits the application and success of hepatic resection for soft-tissue sarcoma, and anything less than complete resection is not indicated.

Pediatric appendectomy.

PURPOSE: To define patterns of care and outcome for pediatric appendectomy. METHODS: A study was designed to evaluate all pediatric appendectomies performed in the 147 Department of Defense hospitals worldwide. Cases of nonincidental appendectomy were identified through discharge diagnoses and operative logs, and 98.6% of the charts were retrieved for review. All charts were abstracted, and data were entered into a 127-field database for analysis. RESULTS: Over a 12-month period, ending January 1993, appendectomy was performed on 1,366 pediatric patients in the Department of Defense hospital system. The patients' median age was 12 years (range, 6 months to 18 years); 59% were male. The diagnosis was normal appendix for 157 patients (12%), acute nonperforated appendicitis for 930 (68%), and perforated appendicitis for 279 (20%). Age < or = 8 years was predictive (P < .001) of a higher rate of perforated appendicitis (33% v 18%) but was not predictive of normal pathology (13% v 11%). Female gender was associated with a significantly higher rate of normal pathology (17% v 8%; P < .001) but not of perforation (18% v 22%). Temperature elevation and right lower quadrant pain and tenderness did not clinically distinguish between diagnostic groups. Sixty-two percent of patients with a normal appendix had a white blood cell count of more than 10,000/mm3, as did 91% of patients with acute or perforated appendicitis. Those with perforated appendicitis received pre- and postoperative antibiotics, primarily ampicillin/gentamicin/clindamycin or Flagyl (41%), cefoxitin (34%), or Unasyn (15%). In 77% of this subgroup, intraoperative cultures were positive, with isolates for Escherichia coli (76%) Enterococcus (30%), Bacteroides (24%), and Pseudomonas (20%) predominating. There were no deaths. Major complications occurred in 1.2% of patients with acute appendicitis and in 6.4% of those with perforated appendicitis; there were no major complications in the group with normal appendectomies. The hospitalization period was more than 7 days for 1.6%, 40%, and 3.8%, respectively. CONCLUSION: This large series, from a large number of hospitals, with multiple practitioners, can serve as a community standard for pediatric appendectomy in the 1990s.

Selective digital enhancement of conventional film mammography.

Screening mammography continues to play a key role in the early diagnosis of non-palpable breast cancer. Approximately 5% of patients will have lesions on their mammograms that appear neither clearly benign nor malignant. The proper management of these patients is not well defined. In this study, the mammograms of 64 women who underwent breast biopsy were reviewed. After the initial review, the mammograms were reevaluated using a personal computer driven digital conversion and enhancement system. The majority of indeterminate lesions were assigned a determinate diagnosis by enhancing the areas of abnormality through enlargement, contrast adjustment, and brightness adjustment. The radiologists were able to maintain baseline sensitivity and specificity throughout this process. In contrast, enhancement of lesions initially assigned a diagnosis of characteristically benign or malignant demonstrated no advantage over plain film mammography. These findings suggest a role for the selective use of digital mammography and enhancement techniques.

Suture granuloma masquerading as malignancy of the biliary tract.

Eighteen years after having a duodenal leiomyosarcoma resected, a patient presented with weight loss, pruritus, and abdominal pain. ERCP was consistent with a cholangiocarcinoma with proximal hepatic duct stricture and nonfilling of the cystic duct. CAT scan revealed no extrinsic masses compressing the gallbladder or biliary tract. At surgical exploration, the patient was found to have a suture granuloma with surrounding fibrosis within the common bile duct. There was no evidence of malignancy.

Management of primary and recurrent soft-tissue sarcoma of the retroperitoneum.

From 1982 to 1987, 114 patients underwent operation at Memorial Sloan-Kettering Cancer Center for soft-tissue sarcoma of the retroperitoneum. A retrospective analysis of these patients defines the biologic behavior, surgical management of primary and recurrent disease, predictive factors for outcome, and impact of multimodality therapy. Complete resection was possible in 65% of primary retroperitoneal sarcomas and strongly predicts outcome (p less than 0.001). The rate of complete resection was not altered by histologic type, size, or grade of tumor. These patients had a median survival of 60 months compared to 24 months for those undergoing partial resection and 12 months for those with unresectable tumors. Forty-nine per cent of completely resected patients have had local recurrence. This is the site of first recurrence in 75% of patients. These patients undergo reoperation when feasible. Complete resection of recurrent disease was performed in 39 of 88 (44%) operations, with a 41-month median survival time after reoperation. Tumor grade was a significant predictor of outcome (p less than 0.001). High-grade tumors (n = 65) were associated with a 20-month median survival time compared to 80 months for low-grade tumors (n = 49). Gender, histologic type, size, previous biopsy, and partial resection versus unresectable tumors did not predict outcome by univariate analysis. Adjuvant radiation therapy and chemotherapy could not be shown to have significant impact on survival. Concerted attempt at complete resection of both primary and recurrent retroperitoneal soft-tissue sarcoma is indicated.

Patterns of cervical node metastases from squamous carcinoma of the larynx.

We undertook a retrospective review of 247 previously untreated consecutive patients from 1965 to 1986 with primary squamous cell carcinoma of the supraglottic or glottic larynx to ascertain the prevalence of neck node metastases by neck level. The 247 patients underwent a total of 262 radical neck dissections. Patients were grouped by clinical neck status at the time of neck dissection: elective dissection in the NO neck; immediate therapeutic dissection in the N+ neck; and subsequent therapeutic dissection in the NO neck that over time converted clinically to N+. Detailed analysis revealed a predominance of neck node metastases in levels II, III, and IV for all clinical neck groups. Level V was rarely involved, but always in conjunction with neck node metastases in levels II, III, or IV (ie, N2 disease). Level I was rarely involved; involvement occurred with neck node metastases in levels II, III, or IV 75% of the time. Level I involvement correlated with T3 or T4 primary tumors exhibiting histologic extralaryngeal spread. These data support the trend toward selective limited neck dissection in both NO and N1 patients.