Inaccurate Staging Research Articles

Probability of false negative nodal staging in conjunction with partial axillary dissection in breast cancer.

There is a risk of overlooking lymph node metastases and thereby contributing to inaccurate nodal staging when performing partial axillary dissection in conjunction with total mastectomy in female breast cancer. The Danish Breast Cancer Cooperative Group (DBCG) analysed this risk in a prospective nation-wide adjuvant trial dealing with primary operable breast carcinoma. The series comprised 3114 patients, initially found to have lymph node negative axillae, followed for a median of 24 months (quartiles 12-40). It was found that the probability of early ipsilateral axillary relapse of cancer, estimated by means of the life table method, decreased with the number of nodes removed. After 2 years the recurrence rate was 12 per cent for patients with no lymph nodes removed, 7 per cent with one or two nodes removed and 2 per cent with three or more nodes removed. It is concluded that the risk of false negative nodal staging in conjunction with partial axillary dissection is modest, provided at least three lymph nodes are removed and found to be negative on histological examination.

Imaging of Penile Neoplasms

The assessment of penile cancer on the basis of clinical findings alone can often result in inaccurate staging and suboptimal treatment. Imaging of primary penile cancer and metastatic lymphadenopathy can help optimize planning of both primary tumor resection and treatment for lymph node metastases. Magnetic resonance (MR) imaging is the most accurate imaging modality in the assessment of primary penile cancers, which usually manifest as solitary, ill-defined infiltrating tumors that are hypointense on both T1- and T2-weighted MR images. T2-weighted MR imaging allows delineation of the tumor margin and of any extension into the penile shaft. On gadolinium-enhanced T1-weighted images, the tumors enhance to a greater extent than do the corpora cavernosa. In addition, the recently introduced technique known as lymphotrophic nanoparticle-enhanced MR imaging can help identify metastatic lymph node disease. However, further studies will be needed to determine the role of this imaging technique in clinical practice. Computed tomography does not clearly depict the local extension of primary penile cancer; however, it is useful in assessing metastases and postoperative complications.

A technically difficult endorectal ultrasound is more likely to be inaccurate

Endorectal ultrasound (ERUS) is well established as an accurate modality for local staging of rectal tumours. The aim of this study was to identify reasons for inaccurate staging of tumours, and to assess whether difficulties encountered during scanning are likely to influence accuracy. ERUS was performed by a single operator using a 10 MHz rigid instrument. One hundred and seventeen patients that had both ERUS and surgery are included in this study (patients that had pre-operative radiotherapy were excluded). During ERUS, procedural conditions and limiting factors were recorded. Data was collected prospectively. In 78 (66.7%) patients no technical difficulty was encountered during ERUS. In this group accuracy was 80% for T-stage and 77% for N-stage. Specific reasons for inaccuracy identified in this group were: inflammatory lymph nodes (from a tumour associated abscess and a colovesical fistula) and deep biopsy causing a submucosal defect with intramural haemorrhage in benign lesions (2 cases). In the remaining 39 (33.3%), the following problems were encountered: stenotic lesions (23), patient discomfort (8), poor bowel preparation (6), and scarring from previous surgery (2). In 11 patients from this group, the scan was considered inconclusive and no stage could be determined. For the other 28, the accuracy for T-stage was 68% and for N-stage 67%. A technically difficult ERUS is likely to give an inconclusive or inaccurate result for both T-stage (P = 0.001) and N-stage (P = 0.003). In this situation a repeat scan may be considered (where appropriate). Alternatively, further assessment by MRI or flexible endoscopic ultrasound may be considered.

Endoscopic ultrasound for esophageal and gastroesophageal junction cancer: Impact of increased use of primary neoadjuvant therapy on preoperative locoregional staging accuracy

Initial treatment of locally advanced esophageal and gastroesophageal junction (GEJ) malignancies for selected patients at some institutions has recently changed from surgical resection to neoadjuvant therapy. The aim of this study is to evaluate the impact of this change in treatment strategy on both the overall disease profile and locoregional endoscopic ultrasound (EUS) staging accuracy for a cohort of patients managed with primary surgical resection over a 10-year period at our institution. All subjects at our institution who underwent primary esophagectomy from 1993 to 2002 following preoperative EUS for known or suspected esophageal and/or GEJ cancers were identified. Patients with dysplasia alone, prior upper gastrointestinal tract surgery, preoperative neoadjuvant therapy, cancer of the gastric cardia or recurrent malignancy were excluded. EUS findings and staging results were compared to surgical pathology following resection. The impact of the gradually increased use of primary chemoradiation during the second half of the study was assessed. Of the 286 operations performed, 184 subjects were excluded. The remaining 102 underwent primary surgical resection a median of 18 days following EUS staging for adenocarcinoma (88%) or squamous cell carcinoma (12%) of the esophagus (69%) or GEJ (31%). Overall EUS locoregional T and N staging accuracy was 72% and 75% respectively; accuracy for T1, T2, T3 and T4 cancer was 42%, 50%, 88% and 50% respectively. Despite an increased frequency of pathologically confirmed T1 and T2 cancers (P = 0.005) and an insignificant trend toward increased N0 malignancy (P = 0.05) during the second half of the study period, no statistically significant changes in T (P = 0.07) or N (P = 0.82) staging accuracies for EUS or disease characteristics were noted between the first and second half of the study period. Despite both inaccurate radial EUS staging and increased relative use of primary surgery for early cancers, recent increased use of primary neoadjuvant therapy did not change overall disease characteristics and accuracy of locoregional EUS staging of esophageal and GEJ cancers managed with primary surgical resection.

Metastatic Renal Cell Carcinoma versus Pancreatic Neuroendocrine Tumor in von Hippel-Lindau Disease: Treatment with Interleukin-2

Differentiating between clear cell neuroendocrine tumor (NET) of the pancreas and renal cell carcinoma (RCC) metastatic to the pancreas can be challenging in patients with von Hippel-Lindau disease (VHL). The clear cell features of both NET and RCC in VHL patients may lead to misdiagnosis, inaccurate staging, and alternative treatment. We present a patient in which this occurred. As clear cell NETs closely resembling metastatic RCC are distinctive neoplasms of VHL and metastatic RCC to the pancreas in the VHL population is rare, careful pathologic examination should be performed prior to subjecting patients to definitive surgical or medical therapies.

Feasibility study of liposomal doxorubicin consolidation therapy after platinum/paclitaxel-based chemotherapy for suboptimally debulked stage IIIC/IV ovarian cancer patients

5044 Background: To assess the utility of liposomal doxorubicin (Doxil) as a consolidation strategy in patients with advanced ovarian cancer who have attained a clinically defined complete response (CR) to initial platinum/paclitaxel-based chemotherapy. Methods: Patients diagnosed with suboptimally debulked Stage IIIC/IV ovarian cancer who attained a clinically defined complete response (CA-125 < 35, normal CT scan, and normal pelvic exam) at the completion of platinum/paclitaxel-based chemotherapy were eligible for this protocol. Patients were treated with Doxil at a dose of 40 mg/m2 every 28 days for four cycles. Primary endpoints included toxicity, quality of life (QoL), and time to progression. Results: Of the 30 patients enrolled, 26 patients are evaluable, three patients are currently being treated, and one patient was ineligible due to inaccurate staging. 22 of the 26 evaluable patients (85%) completed all four cycles of consolidation therapy. Three patients were removed from the study after their 3rd course due to palmar-plantar erythrodysesthesia (PPE) and one for recurrent disease after her 3rd course. 13 patients required a 25% dose modification (11 patients for grade 2/3 PPE and 2 patients for grade 3 myelosuppression). A subset of patients completed a baseline and post-treatment QoL questionnaire and no difference was detected between the baseline and post-treatment QoL scores (p=0.179). Of the 26 patients who completed consolidation therapy, 10 remain clinically without evidence of disease with a median follow-up of 15 months from completion of primary chemotherapy (range, 7–20 months). Sixteen patients have recurred following treatment with a median time to recurrence of 10 months (range, 3–18 months). Conclusions: Consolidation therapy with Doxil chemotherapy administered to women with advanced ovarian cancer who attain a clinically defined complete response to initial chemotherapy appears feasible. PPE is the most common toxicity leading to dose modification and study discontinuation. Impact on progression-free survival awaits additional follow-up. No significant financial relationships to disclose.

Feasibility study of liposomal doxorubicin consolidation therapy after platinum/paclitaxel-based chemotherapy for suboptimally debulked stage IIIC/IV ovarian cancer patients

5044 Background: To assess the utility of liposomal doxorubicin (Doxil) as a consolidation strategy in patients with advanced ovarian cancer who have attained a clinically defined complete response (CR) to initial platinum/paclitaxel-based chemotherapy. Methods: Patients diagnosed with suboptimally debulked Stage IIIC/IV ovarian cancer who attained a clinically defined complete response (CA-125 < 35, normal CT scan, and normal pelvic exam) at the completion of platinum/paclitaxel-based chemotherapy were eligible for this protocol. Patients were treated with Doxil at a dose of 40 mg/m2 every 28 days for four cycles. Primary endpoints included toxicity, quality of life (QoL), and time to progression. Results: Of the 30 patients enrolled, 26 patients are evaluable, three patients are currently being treated, and one patient was ineligible due to inaccurate staging. 22 of the 26 evaluable patients (85%) completed all four cycles of consolidation therapy. Three patients were removed from the study after their 3rd course due to palmar-plantar erythrodysesthesia (PPE) and one for recurrent disease after her 3rd course. 13 patients required a 25% dose modification (11 patients for grade 2/3 PPE and 2 patients for grade 3 myelosuppression). A subset of patients completed a baseline and post-treatment QoL questionnaire and no difference was detected between the baseline and post-treatment QoL scores (p=0.179). Of the 26 patients who completed consolidation therapy, 10 remain clinically without evidence of disease with a median follow-up of 15 months from completion of primary chemotherapy (range, 7–20 months). Sixteen patients have recurred following treatment with a median time to recurrence of 10 months (range, 3–18 months). Conclusions: Consolidation therapy with Doxil chemotherapy administered to women with advanced ovarian cancer who attain a clinically defined complete response to initial chemotherapy appears feasible. PPE is the most common toxicity leading to dose modification and study discontinuation. Impact on progression-free survival awaits additional follow-up. No significant financial relationships to disclose.

Peptide nucleic acid clamp PCR: a novel K-ras mutation detection assay for colorectal cancer micrometastases in lymph nodes.

Inaccurate staging of colorectal cancer (CRC) has been attributed to the failure to detect lymph node metastases by conventional pathology. We have previously reported the use of lymphatic mapping to accurately identify those lymph nodes most likely to harbor micrometastatic disease and permit focused pathologic examination. Mutation of K-ras allele at codons 12 or 13 occurs frequently in early stages of CRC development. The purpose of our study was to assess sentinel lymph nodes (SLN) for occult CRC micrometastases using a unique peptide nucleic acid (PNA) clamp PCR assay specific for K-ras mutations. Seventy-two paraffin-embedded primary CRC and paired SLN were evaluated by PNA clamp PCR for K-ras mutations. Thirty primary tumors (42%) were positive for K-ras mutations, and in 5 of these cases the SLN were positive for metastases by Hematoxylin and Eosin staining. PNA clamp PCR identified occult metastases in an additional 6 patients, upstaging 24% of K-ras positive primary CRCs (p = 0.014). No K-ras mutations were detected among the 20 noncancer lymph nodes assessed. This study demonstrates the utility, specificity and sensitivity of PNA clamp PCR assay in identifying occult micrometastases in the SLN of CRC patients by single-base mutation analysis.

A new prognostic model comprising p53, EGFR, and tumor grade in early stage epithelial ovarian carcinoma and avoiding the problem of inaccurate surgical staging

Epithelial ovarian carcinoma rarely occurs because of a single event. Therefore, no single biological tumor factor will give accurate prognostic information for all ovarian cancer patients. On the other hand, a combination of two or more independent factors may yield an improved overall prognostic index. Because FIGO stage is included in most of the previously presented models, inaccurate surgical staging in patients with apparently early disease has been a problem. In a series of 226 patients with epithelial ovarian carcinomas in FIGO stages IA–IIC, a number of clinicopathological factors (age, FIGO stage, histopathologic type, and tumor grade) were studied in relation to the biological factors p53 and epidermal growth factor receptor (EGFR), important regulators of the apoptosis and mitosis. Immunohistochemical techniques were used. All patients received adjuvant radiotherapy or chemotherapy after the primary surgery. Expression of p53 was significantly associated with the tumor grade and disease-free survival (DFS). EGFR expression was also associated with DFS. In a Cox multivariate analysis, tumor grade, p53 status, and EGFR status were all independent and significant prognostic factors with regard to DFS. A prognostic model was proposed using these factors. A low-risk group, an intermediate-risk group, and a high-risk group were defined. DFS amounted to 89% in the low-risk group (grades 1–2, p53-negative, and EGFR-negative), 66% in the intermediate-risk group (grade 3, p53-negative, and EGFR-negative or grades 1–2, p53-positive or EGFR-positive) and 39% in the high-risk group (grade 3, p53-positive, and EGFR-positive).

Impact of lymph node retrieval and pathological ultra-staging on the prognosis of stage II colon cancer.

A minimum number of lymph nodes must be assessed for accurate diagnosis of stage II colon cancer. We assessed number of lymph nodes retrieved, pathological ultra-staging, and outcome in stage II colon cancer. Consecutively treated patients with stage II colon cancer were identified. Baseline and outcome data were collected. Retrospective ultra-staging using lymphovascular invasion (LVI) and nodal micrometastases was performed. Patients were divided into two groups: group I had <or=6 nodes and group II had >6 nodes retrieved. Survival was analyzed. One hundred and fifteen patients were included in the study. The 5 year overall survival was worse in group I versus II (P = 0.03). LVI and micrometastases were identified but neither predicted survival. Disease failure in group I was due to distant metastases rather than local recurrence. Inadequate retrieval and assessment of lymph nodes is associated with worse outcome in stage II colon cancer patients. Recurrence patterns support the hypothesis that disease recurrence occurred due to inaccurate staging. In this small study, LVI or nodal micrometastases did not predict survival. Maximal attention should be paid to the total number of lymph nodes retrieved before embarking on potentially more resource intensive staging methods.

Staging of esophageal carcinoma

J Thorac Cardiovasc Surg 2003;125:988-91

Can we rely on the size of the lymph node in determining nodal metastasis in ovarian carcinoma?

This study endeavored to determine whether lymph node size is a reliable indicator in determining lymph node metastasis in common epithelial ovarian cancer. We reviewed pathologic sections of pelvic and para-aortic lymph nodes removed from 104 ovarian carcinoma patients who underwent either primary surgical staging or secondary surgery from January 1994 to July 2001. All sections of each individual node were measured in two dimensions. The different sizes of nodes were studied statistically to determine the optimal sensitivity and specificity in predicting cancer metastasis. A nodal size of 10 mm was a specific point of interest. Of 2069 total nodes obtained, 110 nodes (5.3%) had metastatic cancer. More than half (55.4%) of these positive nodes had a nodal long axis of 10 mm and less. The sensitivity and specificity of nodal size at 10 mm were 44.5% and 81.1%, respectively. We conclude that lymph node size is not a good indicator in determining epithelial ovarian cancer metastasis. Mere sampling of only the enlarged nodes does not reflect the true positive incidence of nodal metastasis. To avoid inaccurate staging and improper management, complete lymph node dissection is proposed as part of surgical staging for ovarian cancer.

Can we rely on the size of the lymph node in determining nodal metastasis in ovarian carcinoma?

This study endeavored to determine whether lymph node size is a reliable indicator in determining lymph node metastasis in common epithelial ovarian cancer. We reviewed pathologic sections of pelvic and para-aortic lymph nodes removed from 104 ovarian carcinoma patients who underwent either primary surgical staging or secondary surgery from January 1994 to July 2001. All sections of each individual node were measured in two dimensions. The different sizes of nodes were studied statistically to determine the optimal sensitivity and specificity in predicting cancer metastasis. A nodal size of 10 mm was a specific point of interest. Of 2069 total nodes obtained, 110 nodes (5.3%) had metastatic cancer. More than half (55.4%) of these positive nodes had a nodal long axis of 10 mm and less. The sensitivity and specificity of nodal size at 10 mm were 44.5% and 81.1%, respectively. We conclude that lymph node size is not a good indicator in determining epithelial ovarian cancer metastasis. Mere sampling of only the enlarged nodes does not reflect the true positive incidence of nodal metastasis. To avoid inaccurate staging and improper management, complete lymph node dissection is proposed as part of surgical staging for ovarian cancer.

Increased mortality from breast cancer and inadequate axillary treatment

Background. The assessment of axillary nodal status remains divisive: inaccurate staging may result in untreated axillary disease, and appropriate adjuvant therapy not being delivered. The impact of inadequate axillary treatment on survival remains controversial. We analyse the impact of failure to adequately assess the axillary nodal status on survival. Methods. All women with confirmed breast cancer in a 15-year period were identified, and the original pathology reports examined, and details of radiotherapy obtained. The survival of women by axillary sample size was compared to a reference group of women and corrected for nodal status, tumour size, age, deprivation category and speciality of treating surgeon. Findings. Sampling less than four nodes is associated with a significantly increased risk of death. This cannot be due to understaging the extent of axillary disease nor is fully explainable by differential prescription of adjuvant therapies. We conclude that the survival of the women studied may have been adversely effected by inadequate axillary treatment.

Integration of chemotherapy in early NSCLC

Over 1 300 000 lung cancer deaths have been estimated in the year 2000 [1]. Such enormous fatality rate reflects the limited chance of cure, with a dismal overall 5-year survival of approximately 14% in the United States and only 10% in Europe [2]. Surgical excision is still the most effective way to achieve local control and permanent cure, but is only applicable to 25 /30% of cases due to the tumour burden and tobacco-related comorbidity. It appears from epidemiological trends that major reductions of mortality for this disease can only be achieved by early detection and truly innovative treatments. Induction (neo-adjuvant) chemotherapy emerged as an option for patients with N2 disease after it became clear that only a minority of these patients could benefit from surgical resection alone and that preoperative radiotherapy had no effect on survival [3]. As the ability to perform a complete surgical resection, for locally advanced tumours, seems to play an important role in the management of this disease, a treatment modality that could reduce the tumour burden preoperatively might be useful to achieve a larger number of complete resections. Another potential benefit of induction chemotherapy is the fact that patients tend to be more compliant and less immuno-suppressed prior to surgery than they are in the post-operative period, and the pathological effect of chemotherapy on the tumours can be assessed more accurately, since resection occurs following chemotherapy. Furthermore, induction chemotherapy could eradicate micrometastatic disease, already present at the time of surgery, and thereby prolong survival. Induction chemotherapy followed by surgical resection and radiotherapy has been shown to improve survival in small randomised trials as well as in larger phase II studies [4], when results are compared with historical controls. Three phase III trials tested induction chemotherapy followed by surgery versus primary surgical resection in patients with clinical stage IIIA disease [5 /7]. Although different chemotherapy protocols were used and the number of patients was small, the survival rates reported were significantly higher than in the control arms. However, criticism has been raised on these trials due to patient’s selection, inaccurate staging and very short survival in the non-chemotherapy arm. In less advanced lung cancer, or intrapulmonary disease (T2N0 or T1-2N1 at CT scan), surgery alone can achieve a 40 /50% 5-year survival. Still, nearly half of the patients die because of recurrent disease and the prognosis is poor enough to justify adjuvant therapies. Recent meta-analyses of randomised trials have shown no benefit for postoperative radiotherapy and a limited benefit for cisplatin based postoperative chemotherapy. Large on-going trials in Europe will hopefully clarify the real benefit of adjuvant chemotherapy in operable NSCLC. However, it is invariably true in every experience that chemotherapy, if applied after lung resection, can only be tolerated at full doses by a fraction of randomised patients. Moving chemotherapy upfront has several potential advantages in operable disease: better compliance, earlier treatment of occult residual disease, tumour shrinkage and downstaging leading to a lesser resection volume as well as true pathological assessment of response. Other, more theoretical, benefits include: prevention of viable tumour seeding at the time of surgery and of tumour promotion induced by immunosuppression or growth factors release after major surgery. A recently published trial conducted by the French cooperative group, has showed a nearly significant improvement of survival in patients receiving induction chemotherapy for early stage NSCLC, compared with surgery alone [8]. Some increased toxicity, however, has been observed in the chemotherapy arm, despite the fact that only two cycles of mitomycin containing regimens had been adopted. Given this rationale and scientific background, two multicentric randomised trials have been launched to evaluate two different schemes of preoperative chemotherapy in patients with operable NSCLC (stage E-mail address: ugo.pastorino@ieo.it (U. Pastorino). Lung Cancer 38 (2002) S35 /S36

Inaccurate eus staging of oesophageal cancer: Assessment of causality

Inaccurate eus staging of oesophageal cancer: Assessment of causality

Vernal keratoconjunctivitis.

Vernal keratoconjunctivitis therefore, if managed properly, can be controlled. Inaccurate diagnosis or staging of the disease, together with inaccurate treatment will however, result in changes which can jeopardize sight and may even necessitate corneal surgery at a later date.

Chemotherapy-treated liver metastases mimicking hemangiomas on MR images.

To report the observation that chemotherapy-treated liver metastases may mimic the appearance of hemangiomas on T2-weighted and serial postgadolinium gradient-echo magnetic resonance (MR) images. T2-weighted and serial postgadolinium spoiled gradient-echo images were prospectively and retrospectively analyzed in six patients. All patients had been treated with chemotherapy for a duration of 2-12 months. Histopathologic evaluation of liver lesions was performed in three patients. Twelve lesions that resembled hemangiomas were identified. Lesions were 0.8-5.5 cm in diameter. All were well defined, oval or lobulated, and demonstrated decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images. On immediate postgadolinium images, all lesions demonstrated peripheral nodular enhancement, which coalesced on delayed imaging. Final histopathologic diagnoses were as follows: hepatic metastases from colon cancer (two patients), ovarian cancer (two patients), pancreatic islet cell tumor (one patient), and breast cancer (one patient). Metastases treated by chemotherapy may mimic the appearance of hemangiomas on a variety of commonly employed MR techniques. In patients undergoing MR imaging for the evaluation of liver metastases, a history of prior chemotherapy administration and duration should be sought to prevent inaccurate staging and inappropriate therapeutic decision making.

Prognostic value of positive pleural lavage in patients with lung cancer resection

Background. Despite an early stage, lung cancer patients often have a poor survival, suggesting inaccurate staging. A pleural lavage demonstrating malignant cells at the time of operation may predict a poorer survival, particularly in patients with otherwise early disease. Methods. Patients, with no preoperative evidence of pleural effusions and undergoing a surgical resection with curative intent, had a preresectional and postresectional lavage to be evaluated by cytology. Results. Fourteen percent of patients with stage I disease had malignant cells in their preresectional lavage and had a significantly shorter survival than stage I patients with a negative lavage. Positivity of preresectional lavage was not correlated with nodal status, pleural or lymphatic involvement, or histologic findings. Conclusions. Preoperative pleural lavage should become a standard technique intraoperatively to better characterize and stage patients undergoing lung cancer resections. Patients with malignant cells in their preoperative lavage should be upstaged.

What are the problems associated with the surgical treatment of patients with pancreatic cancer?

Modern surgical therapy of pancreatic cancer has resulted in few long-term survivors. There are several reasons. First, most patients are not diagnosed in an early tumor stage, resulting in a minority of patients undergoing surgical resection. A breakthrough in screening methodology is required until this most major of obstacles can be overcome. Second, inaccurate clinical tumor staging is all that is available for the majority of patients, since most patients are not resected. Imaging techniques used for clinical staging require anatomic verification before clinical staging can be reliable. Then adequate comparison of treatments for patients who never receive anatomical staging can accomplished. Postoperative tumor staging using anatomical methods from intraoperative findings and examination of a surgical specimen require a staging system that is simple and directly correlates with survival. The best staging system can be developed only with international cooperation. An adequate comparison of the results of treatment will then be possible. Two broad treatment areas that are most promising are surgical (extending resections to yield negative surgical margins) and adjuvant protocols (beginning with a variety of radio sensitizing chemotherapeutic agents).