Blake Cady

Surgical margin in hepatic resection for colorectal metastasis: a critical and improvable determinant of outcome.

OBJECTIVE To update the analysis of technical and biologic factors related to hepatic resection for colorectal metastasis in a large single-institution series to identify important prognostic indicators and patterns of failure. SUMMARY BACKGROUND DATA Surgical therapy for colorectal carcinoma metastatic to the liver is the only potentially curable treatment. Careful patient selection of those with resectable liver-only metastatic disease is crucial to the success of surgical therapy. METHODS Two hundred forty-four consecutive patients undergoing curative hepatic resection for metastatic colorectal carcinoma were analyzed retrospectively. Variables examined included sex, stage of primary lesion, size of liver lesion(s), number of lesions, disease-free interval, ploidy, differentiation, preoperative carcinoembryonic antigen level, and operative factors such as resection margin, use of cryotherapy, intraoperative ultrasound, and blood loss. RESULTS Surgical margin, number of lesions, and carcinoembryonic antigen (CEA) levels significantly control prognosis. Patients with only one or two liver lesions, a 1-cm surgical margin, and low CEA levels have a 5-year disease-free survival rate of more than 30%. Disease-free interval, original stage, bilobar involvement, size of metastasis, differentiation, and ploidy were not significant predictors of recurrence. The pattern of failure correlates with surgical margin. Routine use of intraoperative ultrasound resulted in an increased incidence of negative surgical margin during the period examined. CONCLUSIONS Surgical resection or cryotherapy of hepatic metastasis from colorectal cancer is safe and curable in appropriately selected patients. Biologic factors, such as number of lesions and carcinoembryonic antigen levels, determine potential curability, and surgical margin governs the patterns of failure and outcome in potentially curable patients. Optimization of selection criteria and surgical resection margins will improve outcome.

Edema of the arm as a function of the extent of axillary surgery in patients with stage I–II carcinoma of the breast treated with primary radiotherapy

Edema of the arm can be a significant complication following treatment of breast cancer. To determine the risk of arm edema and factors associated with this risk in patients treated with primary radiotherapy, we reviewed the records of 475 women with early breast cancer treated between 1968 and 1980. During this period, the use of axillary surgery prior to radiation gradually increased, and all patients received full axillary irradiation until late in the series. Based on the surgeons report, the extent of axillary surgery was classified as either a sampling, a lower dissection, or a full dissection. Edema of the arm was scored on clinical grounds and ranged from mild hand swelling to an increased arm circumference of 8 cm. At 6 years, the actuarial risk of developing arm edema was 8% for the entire study population. This risk was 13% for 240 patients who had axillary surgery and 4% for 235 patients not undergoing axillary surgery (p = 0.006). For patients undergoing axillary surgery, the risk of arm edema was 37% with full dissection compared to 5% with sampling (p = 0.0003), and 8% with lower dissection (p = 0.03). The risk of arm edema at 6 years was 28% if more than ten nodes were removed, and 9% if one to ten nodes were removed (p = 0.03). However, the extent of axillary dissection was stronger predictor of subsequent edema than was the number of nodes obtained. The role of axillary irradiation could not be evaluated since 91% of patients received axillary irradiation. The use of chemotherapy, the site or size of the primary tumor, clinical nodal status, patient age and weight, type of suture, the use of a drain, and subsequent local or distant failure did not appear to be significant risk factors. We conclude that the combination of full dissection and full axillary irradiation results in an unacceptably high risk of arm edema.

Resection of the liver for colorectal carcinoma metastases. A multi-institutional study of long-term survivors.

In this review of a collected series of patients undergoing hepatic resection for colorectal metastases, 100 patients were found to have survived greater than five years from the time of resection. Of these 100 long-term survivors, 71 remain disease-free through the last follow-up, 19 recurred prior to five years, and ten recurred after five years. Patient characteristics that may have contributed to survival were examined. Procedures performed included five trisegmentectomies, 32 lobectomies, 16 left lateral segmentectomies, and 45 wedge resections. The margin of resection was recorded in 27 patients, one of whom had a positive margin, nine of whom had a less than or equal to 1-cm margin, and 17 of whom had a greater than 1-cm margin. Eighty-one patients had a solitary metastasis to the liver, 11 patients had two metastases, one patient had three metastases, and four patients had four metastases. Thirty patients had Stage C primary carcinoma, 40 had Stage B primary carcinoma, and one had Stage A primarycarcinoma. The disease-free interval from the time of colon resection to the time of liver resection was less than one year in 65 patients, and greater than one year in 34 patients. Three patients had bilobar metastases. Four of the patients had extrahepatic disease resected simultaneously with the liver resection. Though several contraindications to hepatic resection have been proposed in the past, five-year survival has been found in patients with extrahepatic disease resected simultaneously, patients with bilobar metastases, patients with multiple metastases, and patients with positive margins. Five-year disease-free survivors are also present in each of these subsets. It is concluded that five-year survival is possible in the presence of reported contraindications to resection, and therefore that the decision to resect the liver must be individualized.

Changing clinical, pathologic, therapeutic, and survival patterns in differentiated thyroid carcinoma.

Records of 792 patients with differentiated thyroid carcinoma seen at the Lahey Clinic Foundation over a 40-year period were analyzed; 631 patients had a minimum followup period of 15 years. Differentiated types currently constitute nearly 90% of thyroid carcinomas. The clinical presentation has improved substantially through the years, and the results of treatment generally have improved. The per cent of patients with primarily incurable and locally unresectable disease or distant metastases has decreased from 7% before 1950 to 1% currently, and this group resulted in almost one third of the total fatalities and one half of fatalities within the first 5 years after treatment. Clear relationships were demonstrated between older age, men, extraglandular extension, blood vessel invasion, major capsular involvement, multifocal disease, and higher mortality rates. Lymph node metastases were found to exert a protective effect in all categories of disease analyzed, and this effect was directly related to the number of lymph node metastases present such that no deaths occurred in those patients who had more than 10 node metastases. Surgical treatment recommended is subtotal thyroidectomy for patients at high risk of death from disease as defined by combinations of age, sex, and extraglandular extension. Patients at low risk or with small carcinomas can be treated satisfactorily by lobectomy. Lymph node resections should be of a limited type or a modified neck dissection and should be performed only therapeutically. No improvement, as judged by mortality or recurrence rates, could be demonstrated by the use of radiotherapy after surgery, and its use should be discouraged. Thyroid hormone administered for suppression of endogenous thyroid-stimulating hormone production improved mortality rates significantly in patients with papillary and mixed forms of carcinoma in all age groups but did not affect survival in patients with follicular carcinoma of the thyroid.

Risk factor analysis in differentiated thyroid cancer

Six hundred patients with primary differentiated thyroid carcinoma had follow‐up studies for a minimum of 15 years and a maximum of 45 years. Recurrence rate and death rate were significantly different in defined high‐risk and low‐risk groups of patients. These basic risk groups were defined by age and sex alone; low risk consisted of men 40 years of age and younger and women 50 years of age and younger whereas the high‐risk group were older patients. Recurrence and death rates in patients at high risk were 33% and 27% while respective figures for patients at low risk were 11% and 4%. In more recent years these results have shown significant improvement. Basic risk group definition outweighed the effect of pathologic type, local disease extension, type of treatment, and site of recurrence or metastasis. For instance, radioactive iodine cured 70% of patients at low risk with metastatic disease but only 10% of patients at high risk. Less aggressive biologic behavior of thyroid cancer before the age of menopause implies that an estrogen‐rich milieu may alter the effects of initiating and promoting factors in carcinogenesis. It also suggests that therapeutic trials of estrogen be undertaken in progressive metastatic differentiated thyroid cancer. Cancer 43:810–820, 1979.

Role of the Cdc25A phosphatase in human breast cancer

The phosphatase Cdc25A plays an important role in cell cycle regulation by removing inhibitory phosphates from tyrosine and threonine residues of cyclin-dependent kinases, and it has been shown to transform diploid murine fibroblasts in cooperation with activated Ras. Here we show that Cdc25A is overexpressed in primary breast tumors and that such overexpression is correlated with higher levels of cyclin-dependent kinase 2 (Cdk2) enzymatic activity in vivo. Furthermore, in the breast cancer cell line MCF-7, Cdc25A activity is necessary for both the activation of Cdk2 and the subsequent induction of S-phase entry. Finally, in a series of small (< 1 cm) breast carcinomas, overexpression of Cdc25A was found in 47% of patients and was associated with poor survival. These data suggest that overexpression of Cdc25A contributes to the biological behavior of primary breast tumors and that both Cdc25A and Cdk2 are suitable therapeutic targets in early-stage breast cancer.

Factors in the prognosis of gastric lymphoma.

The tumor‐nodes‐metastases (TNM) staging classification for gastric carcinoma was applied to 50 consecutive cases of primary gastric lymphoma. Survival statistics were obtained for each respective stage category and were remarkably similar to survival statistics for gastric carcinoma. Overall, patients with primary gastric lymphoma have a much better prognosis for survival than patients with gastric carcinoma since the latter present with far more frequent serosal penetration and nodal and distant metastases. Penetration of gastric lymphoma beyond the serosa is associated with a significantly decreased 5‐year survival rate from 88 to 24%, and the presence of perigastric nodal involvement decreased the survival rate from 88 to 32%.

The use of radiotherapy for treatment of isolated locoregional recurrence of breast carcinoma after mastectomy

The role of radiotherapy in the treatment of isolated local recurrence of breast cancer after mastectomy is controversial. In an attempt to define this role, the results of moderate‐dose radiotherapy in 90 such patients were reviewed. The median follow‐up time for these patients was 81 months. The actuarial probability of local control after treatment was 42% at 5 years and 35% at 10 years. Freedom from distant failure was 30% at 5 years and only 7% at 10 years. The rate of appearance of distant metastasis was fairly constant at approximately 20% of patients per year. Overall survival was 50% at 5 years and 26% at 10 years. Overall survival and relapse‐free survival were both chiefly influenced by the disease‐free interval (DFI). Patients who presented with a DPI of greater than or equal to 2 years had a 5‐year actuarial overall survival rate of 58% compared to 33% for patients with a DFI of less than 2 years (P = 0.04). Subsequent local failures after radiotherapy were principally seen at the initial site of recurrence, but also at other sites in or at the edge of the radiation fields. These results strongly suggest that patients with apparently isolated local recurrence after mastectomy are incurable by further local treatment. Effective systemic therapy is required to improve the results in these patients. Radiotherapy is a useful palliative procedure in patients with long disease‐free intervals. The role of radiotherapy in conjunction with systemic therapy is, as yet, undefined.

Clinical axillary recurrence in breast cancer patients after a negative sentinel node biopsy

BACKGROUND The purpose of this study was to determine the axillary recurrence rate in breast cancer patients with a negative sentinel lymph node who did not have an axillary node dissection. METHODS Sentinel lymphadenectomy for breast cancer patients, without axillary node dissection if the node was negative, was introduced in 1998 at our institution. This study includes those women with a negative sentinel lymph node. Adjuvant chemotherapy was administered based on primary tumor characteristics. If breast radiotherapy was used, no attempt was made to include the axilla. RESULTS From January 1998 to December 2001, 206 patients (208 breast cancers) had a negative sentinel lymph node. The median age at diagnosis was 56 years and median tumor size was 1.2 cm. With a median follow-up of 26 months, there have been 3 axillary recurrences with a clinical sentinel lymph node false negative rate of 1.4%. CONCLUSIONS In this study, the clinical false negative rate of a sentinel lymph node biopsy is 1.4%. Our study provides further evidence supporting the use of sentinel lymphadenectomy in women with breast cancer.

Results of treating ductal carcinoma In situ of the breast with conservative surgery and radiation therapy

To determine the frequency, pattern, and time course of tumor recurrence in the breast, the outcome of 38 women with ductal carcinoma in situ (DCIS) treated with conservative surgery and radiation therapy between 1976 and 1985 was studied. Surgery typically consisted of local excision without evaluation of the microscopic margins of resection. The median radiation dose to the tumor site was 6400 cGy. With a median follow‐up time of 81 months, eight patients (21%) have experienced a recurrence in the breast. The time course to recurrence was protracted in some cases, with failures occurring at 17, 27, 43, 63, 71, 83, 92, and 104 months. The 5‐year and 8‐year actuarial rates of tumor recurrence in the breast were 8% and 27%, respectively. Seven patients had a recurrence at or near the primary tumor site, four with invasive carcinoma, and one had an invasive recurrence at a site elsewhere in the breast. No clinical or pathologic factor was significantly associated with an increased risk of recurrence, but the number of patients in the study population was small. The authors reached the following conclusions for patients with DCIS treated with conservative surgery and radiation therapy without careful mammographic and pathologic evaluation: (1) recurrence in the breast may be seen in at least one fifth of the patients; (2) recurrence typically occurs at or near the primary site; and (3) recurrence can occur long after treatment. Careful mammographic and pathologic assessment may be useful in reducing the local recurrence rate and should be considered essential if patients are considered for conservative surgery and radiation therapy.