Effects of multidisciplinary interventions on weight loss and health outcomes in children and adolescents with morbid obesity.

OBJECTIVE: Morbid obesity is the fastest growing subcategory of childhood obesity, associated with an increased health risk that persists into adulthood. There is an urgent need to develop multifaceted interventions that target initial and long-term lifestyle changes. This review investigates the effects of multidisciplinary interventions on weight loss and health outcomes in children and adolescents with morbid obesity. The influence of age, gender and family participation on health outcomes and intensive treatment alternatives are explored. METHODS: The review includes 16 studies conducted between 1995 and 2017. Studies examined youth with morbid obesity, 4-18 years old, undergoing multidisciplinary treatment. RESULTS: All studies found a reduction in body mass index (BMI or z-score) and if measured, cardiovascular risk factors. Physical activity, nutrition education, behavioural modification and family involvement are commonly included treatment components and have improved weight loss and health-related outcomes. However, initial weight loss was often not sustainable, despite the favourable interventional effect on cardiometabolic risk markers. Weight loss was prolonged in younger children and among the male sex. CONCLUSIONS: There is not a 'one-size-fits-all' treatment approach, and matched care to personal needs is preferable. The integration of a chronic care approach is critical for the successful adaption of sustainable health behaviours.

Complete metabolic remission of an irresectable mediastinal solitary fibrous tumour with concurrent chemoradiation.

Solitary fibrous tumour is a rare mesenchymal tumour of uncertain origin that occurs most frequently in the pleura, although it has also been described in extraserosal sites. The biological behaviour of the tumour is unpredictable. The case history is described of a patient diagnosed with a large symptomatic irresectable mediastinal solitary fibrous tumour who achieved a clinical, radiological and metabolic response after concurrent chemotherapy and radiotherapy.

Unclassified rhabdomyosarcoma in a patient with anti-Hu syndrome.

Anti-Hu syndrome is a paraneoplastic neurological syndrome, most frequently associated with small cell carcinoma of the lung. Subacute sensory neuronopathy is thought to be the most frequent presentation of the anti-Hu syndrome, but it seems that sensory-motor neuropathy is the most common form in the anti-Hu neuropathy. Neurological symptoms often appear before the associated cancer has been identified. Sometimes the tumor is discovered months or even a few years after the appearance of the neurological syndrome. FDG-PET scan seems a better method for finding the tumor in patients with paraneoplastic neurological syndrome and anti-Hu antibodies who had negative test results after an initial workup using radiological methods. In this case report we present a patient with the anti-Hu syndrome associated with an unclassified rhabdomyosarcoma with epitheloid cellular morphology and neuroendocrine differentiation.

Influence of age, comorbidity and performance status on the choice of treatment for patients with non-small cell lung cancer; results of a population-based study.

BACKGROUND: In the Netherlands in 1997, 43% of patients with newly diagnosed lung cancer were over 70. Large age-specific differences in treatment exist. We examined whether age, comorbidity, performance status and pulmonary function influenced treatment. PATIENTS AND METHODS: Data on patients with newly diagnosed non-small cell lung cancer (N = 803) were obtained: comorbidity, performance status, pulmonary function (FEV1) and initial treatment. Age-specific differences in treatment according to the guidelines were examined. Odds ratios were calculated by means of logistic regression analyses. RESULTS: 82% with stage I or II disease received treatment according to the guidelines; this applied to 48% with stage IIIA disease and to 54% with stage IIIB disease. For all stages, this proportion decreased with increasing age. In stage IV disease, 36% did not receive any treatment; this applied to 52% of the elderly patients (75+ years). Multivariate analyses showed associations between comorbidity and treatment choice, but none with performance status. Age of 75+ years appeared to be the most important factor for not receiving treatment according to guidelines. CONCLUSION: A substantial proportion of elderly patients with non-small cell lung cancer did not receive standard treatment. Performance status and comorbidity seldom formed the underlying reason. Calendar rather than biological age seemed to play the most important role in choice of treatment for patients with non-small cell lung cancer.

MR-imaging of the brain of neurologic asymptomatic patients with large cell or adenocarcinoma of the lung. Does it influence prognosis and treatment?

Magnetic resonance imaging (MRI) of the brain and extensive neurological examination by a neurologist was performed as part of initial staging evaluation of 91 neurologic asymptomatic patients with large cell carcinoma or adenocarcinoma of the lung. Patients were followed up for at least 6 months. Evidence of metastatic brain disease was documented in 13 (14%) patients. Two of these patients were found suspective of brain metastases (BM) by the neurologist. The detection of BM resulted in upstaging of 1 (3%) patient in stage I/II, 4 (21%) patients in stage IIIA and 2 (11%) patients in IIIB. Especially for patients in stage III this upstaging is of importance as aggressive locoregional treatment can be abandoned. Evaluation of the brain with MRI is a sensitive method of detecting BM in neurologic asymptomatic patients and is recommended as part of the initial staging of patients with large cell carcinoma or adenocarcinoma of the lung in stage III. Additional examination by the neurologist is of little value to provide information of the neurologic status.

Docetaxel as neoadjuvant therapy for radically treatable stage III non-small-cell lung cancer: a multinational randomised phase III study.

BACKGROUND: Docetaxel (Taxotere) is a potent anticancer agent, with proven efficacy as first-line therapy in non-small-cell lung cancer (NSCLC). The aim of this large randomised multicentre phase III study was to evaluate docetaxel in the neoadjuvant (pre-operative) setting. PATIENTS AND METHODS: Patients with stage IIIA or locally treatable IIIB NSCLC were randomly assigned to receive neoadjuvant docetaxel (n = 134) or no chemotherapy (n = 140) before surgery/curative-intention radiotherapy. Patients received up to three 3-weekly cycles of docetaxel (100 mg/m(2)) as 1-h intravenous infusions. RESULTS: Median survival was 14.8 months in the docetaxel group and 12.6 months in the control group. Median times to disease progression were 9.0 months (docetaxel arm) and 7.6 months (control arm). There were three complete responses and 25 partial responses in patients treated with docetaxel who were evaluable for response (n = 101). Docetaxel was well-tolerated: 103 patients (77%) received all three planned cycles. The major toxicity was grade 4 neutropenia (69 patients, 55%) and neutropenic fever (eight patients, 6%). Radiotherapy was well-tolerated after docetaxel administration. CONCLUSIONS: Neoadjuvant docetaxel is generally well-tolerated and shows a promising trend towards longer survival in patients with NSCLC.

Prospective study on quality of life before and after radical radiotherapy in non-small-cell lung cancer.

PURPOSE: The purpose of this study was to investigate changes in respiratory symptoms and quality of life (QoL) in patients with non-small-cell lung cancer (NSCLC) receiving radical radiotherapy (60 Gy). Additionally, the association between the level of symptom relief and objective tumor response, as well as with radiation-induced pulmonary changes, was investigated. PATIENTS AND METHODS: One hundred sixty-four patients were entered onto this prospective study. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and EORTC QLQ-LC13 were used to investigate changes in QOL: Assessments were performed before radiotherapy and 2 weeks, 6 weeks, 3 months, 6 months, and 12 months after the completion of radiotherapy. RESULTS: The QoL response rates were excellent for hemoptysis (83%); good for chest pain (68%), arm/shoulder pain (63%), and appetite loss (60%); and poor for dyspnea (37%), cough (31%), and fatigue (28%). The QoL response rates for the five functioning scales of the QLQ-C30 varied from 35% for physical and role functioning to 55% for social and cognitive functioning. The response rate for global QoL was 36%. A significant association was found between tumor response and palliation of chest pain, arm/shoulder pain, and physical functioning. During radiotherapy, a significant increase for most general symptoms and a deterioration in functioning and QoL were noted. CONCLUSION: This study is the first to describe palliation and changes in QoL in radically irradiated patients with NSCLC. Radical radiotherapy offers palliation of respiratory symptoms and improved QoL in a substantial proportion of patients with NSCLC who have relatively good prognostic features. Although tumor reduction is associated with palliation of respiratory symptoms, it cannot serve as a surrogate for palliation.

Diagnostic yield of computed tomography and densitometric measurements of the lung in thoracoscopically-defined idiopathic spontaneous pneumothorax.

In the present study, the diagnostic yield of high resolution computed tomography (HRCT) is evaluated in patients with thoracoscopically-verified idiopathic spontaneous pneumothorax (SP). Visual assessment as well as densitometry of lung parenchyma was performed. In eight of the 20 prospectively-evaluated SP patients, emphysema-like (EL) changes such as blebs and bullae could be detected. The SP patients with EL changes were significantly older and were more heavy smokers. Spirometrically-controlled CT lung densitometry showed no differences between the patient group with or without these EL changes. Comparing the densitometric measurements of the patient group with a healthy control group no significant differences in densitometry between both groups were found. In conclusion, this study confirms that HRCT is a reliable method of detecting blebs and bullae in patients with spontaneous pneumothorax. Furthermore CT lung densitometry revealed no parenchymal abnormalities or signs of air trapping in patients with spontaneous pneumothorax.

External irradiation versus external irradiation plus endobronchial brachytherapy in inoperable non-small cell lung cancer: a prospective randomized study.

PURPOSE: No randomized studies are available on the additional value of endobronchial brachytherapy (EBB) to external irradiation (XRT) regarding palliation of respiratory symptoms (RS). A prospective randomized study was initiated to test the hypothesis that the addition of EBB to XRT provides higher levels of palliation of dyspnea and other RS and improvement of quality of life (QoL) in patients with non-small cell lung cancer (NSCLC) with endobronchial tumour. MATERIALS AND METHODS: Patients with previously untreated NSCLC, stages I-IIIb, WHO-performance status of 0-3 and with biopsy proven endobronchial tumour in the proximal airways were eligible. EBB consisted of two fractions of 7.5 Gy at 1 cm on day 1 and 8. XRT started at day 2. The XRT dose was 30 Gy (2 weeks) or 60 Gy (6 weeks). The EORTC QLQ-C30 and QLQ-LC13 were assessed before treatment and 2 weeks, 6 weeks, 3, 6 and 12 months after treatment. Re-expansion of collapsed lung was tested by the inspiratory vital capacity (IVC) and CT scan of the chest. RESULTS: Ninety-five patients were randomized between arm 1 (XRT alone) (n=48) or arm 2 (XRT+EBB) (n=47). The arms were well balanced regarding pre-treatment characteristics and QoL scores. The compliance for QoL-assessment was >90% at all times. No significant difference between the trial arms was observed with respect to response of dyspnea. However, a beneficial effect of EBB was noted concerning the mean scores of dyspnea over time (P=0.02), which lasted for 3 months. This benefit was only observed among patients with an obstructing tumour of the main bronchus. A higher rate of re-expansion of collapsed lung was observed in arm 2 (57%) compared to arm 1 (35%) (P=0.01). The inspiratory vital capacity (IVC) assessed 2 weeks after radiotherapy improved with 493 cm(3) in arm 2 and decreased 50 cm(3) in arm 1 (P=0.03). No difference was noted regarding the incidence of massive haemoptysis (13 vs. 15%). CONCLUSION: The addition of EBB to XRT in NSCLC is safe and provides higher rates of re-expansion of collapsed lung resulting in a transient lower levels of dyspnea. This beneficial effect was only observed among patients with obstructing tumours in the main bronchus.

Asymptomatic brain metastases (BM) in small cell lung cancer (SCLC): MR-imaging is useful at initial diagnosis.

PURPOSE: In this study we evaluated the usefulness of MR-imaging in the detection of asymptomatic brain metastases (BM) at the initial diagnosis in patients with small cell lung cancer (SCLC) and studied the follow-up of these patients. PATIENTS AND METHODS: One-hundred and twenty-five patients with SCLC were investigated with MR-imaging. RESULTS: In 112 patients with normal neurological findings, MR-imaging of the brain demonstrated BM in 17 patients (15%). Six of these 17 patients were therefore upgraded to extensive disease (ED). Two of these 17 patients died during chemotherapy because of progressive disease and 3 patients became neurologic symptomatic with progressive disease on MR-imaging of the brain. After completion of chemotherapy a repeated MR-imaging of the brain in the remaining 12 patients showed 1 complete remission, 4 partial remission and 7 progressive disease of the BM. CONCLUSION: This study showed that at presentation an unexpectedly high percentage of SCLC patients had asymptomatic BM on MR-imaging. We propose that MR-imaging of the brain should be included in the staging of SCLC patients as well for staging, prognosis and therapy.

Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer.

PURPOSE: New effective chemotherapy is needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC. PATIENTS AND METHODS: Between January 1995 and April 1996, 414 patients with stage IIIB or IV NSCLC were randomized to received either a control arm of high-dose cisplatin (100 mg/m(2)) or a combination of paclitaxel (175 mg/m(2), 3-hour infusion) and cisplatin (80 mg/m(2)) every 21 days. RESULTS: Compared with the cisplatin-only arm, there was a 9% improvement (95% confidence interval, 0% to 19%) in overall response rate for the paclitaxel/cisplatin arm (17% v 26%, respectively; P=.028). Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm, respectively (P=.026). The study, however, failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm (8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm, P=.862). There was more hematotoxicity, peripheral neuropathy, and arthralgia/myalgia on the paclitaxel/cisplatin arm, whereas the high-dose cisplatin arm produced more ototoxicity, nausea, vomiting, and nephrotoxicity. Quality of life (QOL) was similar overall between the two arms. CONCLUSION: This large randomized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC. However, the paclitaxel/cisplatin combination did produce a better clinical response, resulting in an increased time to progression while providing a similar QOL.

Cell proliferation and apoptosis in stage III inoperable non-small cell lung carcinoma treated by radiotherapy.

PURPOSE: The purpose of this study was to assess the prognostic value of the expression of p53 and bcl-2, the apoptotic index and the expression of topoisomerase II alpha in patients with inoperable non-small cell lung cancer (NSCLC) treated with high dose radiotherapy. PATIENTS AND METHODS: A number of 161 patients with inoperable NSCLC treated with high dose radiotherapy (60 Gy) were included. Immunohistochemical analysis was used to assess the expression of nuclear p53-protein, topoisomerase II alpha and cytoplasmatic expression of bcl-2, while spontaneous apoptosis was assessed using in situ labeling. The minimal follow up period was 2 years. RESULTS: Local control did not only depend on the presence of p53 expression, but also on the proportion of p53 positive cells. The most important prognostic factor was the apoptotic index. A high apoptotic index was associated with worse local control, more distant metastases and a significantly worse overall survival. No association was noted between the expression of bcl-2 and topoisomerase II alpha with any of the endpoints. CONCLUSION: This study indicates that p53 expression and the apoptotic index are prognostic factors with regard to local control in patients with inoperable NSCLC treated with radiotherapy and by combining these 2 factors, a clinically relevant estimation of the local control probability can be made. The apoptotic index turned out to be the only factor significantly related to survival.

Early non-elective readmission for chronic obstructive pulmonary disease is associated with weight loss.

AIM: To identify risk factors for early nonelective readmission in patients with chronic obstructive pulmonary disease, previously admitted for an exacerbation of their disease. Clinical characteristics were analysed with special emphasis on body weight on admission and weight changes during hospitalization. METHODS: The computerized hospital database was used to select all hospital admissions in 1994 and 1995 with exacerbation of chronic obstructive pulmonary disease as main discharge diagnosis. Cases were retained if they were nonselectively readmitted within 14 days after prior discharge, and if they had no oedema. Controls were randomly selected from the discharge listing and were not readmitted within 3 months. Cases and controls were matched on several parameters including FEV(1)% predicted obtained during a stable phase of the disease. Hospital charts were reviewed for clinical parameters on admission, discharge and readmission. RESULTS: Fourteen cases were retained in the study. On admission, lung function, blood gases and parameters describing morbidity and social factors, were not different in cases and controls. The discharge procedure was adequate. During hospitalization the cases lost weight (mean+/-SD) (-1.6+/-1.9 kg, P= 0.01), while controls remained weight stable. Using a matched pairs logistic regression analysis, weight loss during hospitalization (P= 0.011) and low BMI on admission (P= 0. 046) were related to the increased risk of unplanned readmission. CONCLUSION: These findings provide further support for the concept that nutritional status is related to morbidity in COPD.

The prognostic impact of quality of life assessed with the EORTC QLQ-C30 in inoperable non-small cell lung carcinoma treated with radiotherapy.

PURPOSE: The purpose of this study was to assess the prognostic significance of pretreatment quality of life (QoL) scores and symptom scores in a group of patients treated with high dose radiotherapy. MATERIAL AND METHODS: A total of 198 patients treated with external irradiation (>/=60 Gy) were included. In all these patients, baseline QoL was assessed using the EORTC QLQ-C30. The prognostic significance of a number of non-QoL and QoL parameters with regard to survival was estimated in both univariate and multivariate analyses. RESULTS: In a multivariate model including the non-QoL parameters, performance status, weight loss and N-classification were independent prognostic factors for survival. After entering the QoL parameters in the model, global QoL was the strongest prognostic factor, while performance status lost its significance. Subsequently, a significant interaction term was found between N-classification and global QoL, indicating that global QoL was an independent prognostic factor but that the effect varied as a function of N-status. In N+ patients, the median survival in the group with low scores for global QoL was 4.5 months, which was significantly worse (P<0.0001) compared with the high score group in which the median survival was 12.9 months. CONCLUSION: Global QoL is a strong prognostic factor for survival in patients with NSCLC who have pathological lymph nodes at presentation and who are treated with radical or curative radiotherapy.

Quality of life after palliative radiotherapy in non-small cell lung cancer: a prospective study.

PURPOSE: The purpose of this study was to investigate changes in respiratory symptoms and quality of life (QoL) in patients with locally advanced and metastatic non-small cell lung cancer (NSCLC) receiving thoracic radiotherapy. Additionally, the correlation between the level of symptom relief and objective tumor response was investigated. METHODS AND MATERIALS: Sixty-five patients were entered in this prospective study. The EORTC QLQ-C30 and EORTC QLQ-LC13 were used to investigate changes in QoL. Assessments were performed before radiotherapy and 2 weeks, 6 weeks, and 3 months after radiotherapy. RESULTS: The QoL response rates were excellent for hemoptysis (79%); good for arm/shoulder pain (56%), chest wall pain (53%), and cough (49%); moderate for dyspnea (39%); and minimal for the general symptoms fatigue (22%) and appetite loss (11%). The QoL response rates for the five functioning scales of the QLQ-C30 varied from 35% for role functioning to 57% for emotional functioning. Global QoL improved in 37% of the cases. In general, there was a tendency for better palliation of symptoms and improvement of QoL among patients with an objective tumor response than among those without objective tumor response, which was statistically significant for dyspnea (p = 0.02) and social functioning (p = 0.04). CONCLUSIONS: This study confirms that conventional thoracic radiotherapy offers palliation of respiratory symptoms and improved QoL in a substantial proportion of patients with locally advanced and metastatic NSCLC. Tumor reduction is only one of the mechanisms by which palliation of symptoms and improvement of QoL is achieved.

Pretreatment quality of life of inoperable non-small cell lung cancer patients referred for primary radiotherapy.

This study examined the association between the most important prognostic factors in non-small cell lung carcinoma (NSCLC) and self-reported pretreatment quality of life (QoL) and the impact of the presence, severity and changes in respiratory symptoms on general symptoms and QoL. The study included 262 patients. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-LC13 were used to assess symptoms and QoL before radiotherapy. Patients with inoperable NSCLC showed major differences in self-reported QoL as a function of clinical prognostic factors. A significant association was found between World Health Organization (WHO) performance status and QoL but not other prognostic factors. Dyspnoea was the only respiratory symptom associated significantly with general symptoms, physical and psychosocial functioning and QoL. Furthermore, changes in dyspnoea were associated significantly with changes in physical and role functioning, global QoL and fatigue as assessed 6 weeks after radiotherapy. These results indicate that palliation of dyspnoea may have a significant beneficial effect on QoL and that palliation of other respiratory symptoms is not necessarily associated with improvement of general symptoms, physical and psychological functioning or global QoL.

Anti-Hu antibody titre and brain metastases before and after treatment for small cell lung cancer.

OBJECTIVES: To follow up the level of anti-Hu antibody titres during chemotherapy and to compare the pattern of metastases and other neurological complications before and after chemotherapy in patients with small cell lung cancer (SCLC) with and without low titre anti-Hu antibodies. Seventeen per cent of patients with SCLC without paraneoplastic syndromes have a low titre of anti-Hu antibodies in their serum. Previous studies suggested that these antibodies correlate with a more indolent tumour growth. METHODS: The serum of 52 consecutive patients with SCLC were studied before and during chemotherapy, and the correlation with stage of disease and pattern of metastases was examined. All serum samples were investigated using western blot and enzyme linked immunosorbent assay (ELISA) with HuD recombinant protein. All patients with SCLC were investigated using MRI of the brain, CSF, bone marrow aspiration, ultrasound of the abdomen, and radionuclide bone scan. RESULTS: Nine (17%) of 52 SCLC serum samples were positive by western blot. At the time of diagnosis none of the anti-Hu positive patients had either CNS (brain or leptomeningeal), epidural, adrenal, or bone marrow metastases and 56% had limited disease. In eight of 43 anti-Hu negative patients CNS metastases were found at the time of diagnosis, and only 30% had limited disease. The prevalence of bone and liver metastases was similar in both groups. Survival was 11 (SD ) months for the 43 anti-Hu negative and 10 (SD 6) months for the nine anti-Hu positive patients. Male:female ratio in the anti-Hu negative group was 4.4:1, and in the anti-Hu positive group 2:1. CONCLUSIONS: No anti-Hu antibody positive serum, as tested by western blot, became negative during chemotherapy. Anti-Hu positive and anti-Hu negative patients had similar survival, but anti-Hu positive patients tended to be women, had limited disease at the time of tumour diagnosis, and initially metastases seemed to spare the nervous system.

Bioelectrical impedance analysis to assess changes in total body water in patients with cancer.

Predominantly based on studies in obese individuals, the applicability of single-frequency bioelectrical impedance analysis (BIA) to measure changes in total body water and fat-free mass has been questioned. To further clarify this issue, we compared changes in BIA-derived height(2)/resistance (ht(2)/R) with changes in total body water (deuterium dilution, delta-TBWdeu) in cancer patients participating in a clinical trial. Thirty-three patients (mean body mass index 23.2 +/- 3.5 kg/m(2)) were studied after an average follow-up of 11 weeks. Changes in TBWdeu occurred in both directions (mean +0.2 +/- 1.6 L, range -3.3 to +3.1 L). These changes were significantly predicted by changes in ht(2)/R (r(2)0.43, P < 0.0001, SEE 1.22 L), although precision was poor (residual SD 1. 2 L). There were in this regard no significant differences between patients with and without underweight. We conclude that in underweight and normal-weight cancer patients, BIA-derived changes in ht(2)/R significantly predict changes in total body water assessed by deuterium dilution.

Clinical value of DNA image cytometry in effusions with atypia.

Malignant cells in serosal effusions provide essential information about the extent of malignant disease. The main aim of this study was to examine the additional diagnostic value of DNA image cytometry for cases with uncertainty in the cytological diagnosis. In addition, the feasibility of automated nuclei detection was investigated. Out of 457 cases, 33 samples in 32 patients were diagnosed with "atypia" (probably benign) and 21 as "suspicious for malignancy." DNA image cytometry was performed on these 54 cases and on an additional group of 14 cytologically malignant cases. The results show that automatic classification is useful for separation of control cells, i.e., lymphocytes and neutrophilic granulocytes from other mononuclear cells. In 21 cases an insufficient number of control cells were measured. Seventy-two percent of the cytologic malignant cases were aneuploid. In contrast, in none of the cases with "atypia" and in only 2 of the cases "suspicious for malignancy" was aneuploidy present (2 of the remaining 32, 6%). From the cases with follow-up, a malignancy in the pleural fluid was present in 2 out of 17 cases with "atypia" and in 5 out of 10 with a "suspicious for malignancy" cytologic diagnosis, respectively. In conclusion, the additional diagnostic value of DNA image cytometry in cases with a cytological diagnosis of "atypia" or "suspicious for malignancy" is limited. Diagn. Cytopathol. 1999;21:112-116.