James F. Huth

Circulating Tumor Cells in Patients with Breast Cancer Dormancy

Purpose: The purpose of this study was to test the hypothesis that circulating tumor cells (CTCs) are present in patients many years after mastectomy without evidence of disease and that these CTCs are shed from persisting tumor in patients with breast cancer dormancy. Experimental Design: We searched for CTCs in 36 dormancy candidate patients and 26 age-matched controls using stringent criteria for cytomorphology, immunophenotype, and aneusomy. Results: Thirteen of 36 dormancy candidates, 7 to 22 years after mastectomy and without evidence of clinical disease, had CTCs, usually on more than one occasion. Only 1 of 26 controls had a possible CTC (no aneusomy). The statistical difference of these two distributions was significant (exact P = 0.0043). The CTCs in patients whose primary breast cancer was just removed had a half-life measured in 1 to 2.4 hours. Conclusions: The CTCs that are dying must be replenished every few hours by replicating tumor cells somewhere in the tissues. Hence, there appears to be a balance between tumor replication and cell death for as long as 22 years in dormancy candidates. We conclude that this is one mechanism underlying tumor dormancy.

Pulmonary resection for metastatic sarcoma

Surgical resection plays an important role in the treatment of sarcoma that is metastatic to the lung. Multiple bilateral metastases are not contraindications to surgery. The rapidity of growth and the response to chemotherapy can be accurately determined by the tumor doubling time. Preoperative chemotherapy provides an in vivo measurement of tumor sensitivity, and the response to chemotherapy correlates with prognosis. Since residual microscopic pulmonary disease appears to be responsible for most failures after thoracotomy, attention should be directed toward delivering more effective adjuvant therapy to the lungs.

Accuracy and effectiveness of laparoscopic vs open hepatic radiofrequency ablation

BackgroundThe purpose of this study was to compare the accuracy (in terms of ultrasound-guided probe placement) and the effectiveness (in terms of pathologic tumor-free margin) of laparoscopic vs open radiofrequency (RF) ablation.MethodsUsing a previously validated tissue-mimic model, 1-cm simulated hepatic tumors were ablated in 10 pigs randomized to open or laparoscopic techniques. Energy was applied until tissue temperature reached 100°C (warm-up) and thereafter for 8 min. A pathologist blinded to technique examined all specimens immediately after treatment. Analysis was by Fisher’s exact test and the Mann-Whitney U test; p<0.05 was considered significant.ResultsOff-center distance (3.5±1.6 vs 4.2±1.4 mm), size (24.7±3.1 vs 25.6±3.8 mm), symmetry (40% vs 73%), margin positivity (33% vs 9%), and margin distance (1.1±1.2 vs 2.2±1.6 mm) were not significantly different between laparoscopic (n=15) and open (n=11) ablations, respectively. The proportion of round/ovoid lesions (20% vs 64%) was lower (p=0.043), and warm-up time (20.2±14.0 vs 10.7±7.5) was longer (p=0.049) for the laparoscopic than for the open groups, respectively.ConclusionAccurate probe placement can be achieved using laparoscopic and open RF ablation techniques. The physiologic effects of laparoscopy may alter ablation shape and warm-up time. Additional studies are needed to establish effective ways of achieving complete tumor destruction.

Abdominosacral resection for malignant tumors of the sacrum

Malignant sacral tumors present unique problems because of their location deep in the pelvis, their juxtaposition to the ureters, rectum, and iliac vessels, and the need to preserve spinal stability and sacral nerve function after resection. The simultaneous abdominosacral resection circumvents many of these problems since it provides good exposure of the intraabdominal structures, allows precise selection of the level of sacral resection, and avoids damage to the sacral nerve roots. Tolerable control of bladder and bowel functions is possible by preservation of the S1 nerve roots, and spinal stability can be maintained with preservation of the body of the S1 vertebra. Because malignant tumors of the sacrum have a high propensity for local recurrence, we believe that the exposure afforded by the sacroabdominal approach provides an opportunity to obtain a wide margin of resection during initial resection of these tumors.

EFFECT OF ACUTE ETHANOLISM ON THE HOSPITAL COURSE AND OUTCOME OF INJURED AUTOMOBILE DRIVERS

Acute ethanolism in automobile drivers is purported to be both protective and detrimental in susceptibility to injury from an accident. The potential influence of acute intoxication (serum ethanol greater than 100 mg/dl) on pattern and severity of injury, hospital course, and long-term outcome, including mortality, was examined in 182 consecutive automobile drivers requiring admission to a regional university trauma center during 1980. Significantly more drivers were intoxicated than not, 61% vs. 39%. Similarly, more than 75% of the intoxicated drivers were young males and more than 80% of the intoxicated drivers were felt to be negligent and at cause for the accident. However in this series, the patterns and severity of injuries, hospital course, and late outcome were unaffected by the patients blood alcohol level. Acute alcohol intoxication apparently neither protected nor hindered the response to injury in these motor vehicle drivers.

Limitations of the Gail Model in the Specialized Breast Cancer Risk Assessment Clinic

The Gail model is a risk assessment tool that is accurate for general breast cancer risk screening. Because of the limited way that this model incorporates family history information, however, there are concerns that it may underestimate risk for many women attending specialized breast cancer risk assessment clinics. We collected comprehensive breast cancer risk factor information for 213 women attending a specialized breast cancer risk assessment clinic using a modified version of the CancerGene software. Breast cancer risk was calculated using the models of Gail and Claus as well as BRCAPRO and the tables of Bodian (for women with lobular neoplasia). Eighty‐six percent of the women had a family history of breast cancer. Although 74% of women had risk factor histories that are thought to confound the Gail model (family history of breast cancer in second‐degree relatives, family history of breast cancer before the age of 50, family history of bilateral breast cancer, family history of ovarian cancer, or personal history of lobular neoplasia), the inclusion of other models increased the risk level assignment in only 13% of the cases. We conclude that the Gail model is an appropriate risk assessment tool for most women attending specialized clinics, although the inclusion of models better able to account for family history information and personal history of lobular neoplasia is required to accommodate all women.

A randomized prospective trial using postoperative adjuvant chemotherapy (adriamycin) in high-grade extremity soft-tissue sarcoma

From March 1981 to December 1984 119 patients with primary grade III extremity soft-tissue sarcoma were randomized postoperatively to single agent Adriamycin (57) or to control, no adjuvant chemotherapy (62). Adjuvant therapy was begun within 6 weeks of surgery, and consisted of Adriamycin 90 mg/m2 given over 2 days, once a month for 5 months. All patients had received preoperative intraarterial Adriamycin, radiation therapy (1,750 cGy) and subsequent surgical excision. At a median follow-up of 28 months there was no difference between the two groups in overall survival (Adriamycin = 84%, control = 80%), local tumor recurrence, or in the disease-free survival (Adriamycin = 58%, control = 54%). This study indicates that the use of single-agent Adriamycin as postoperative adjuvant chemotherapy has no significant clinical benefit in patients with high-grade extremity softtissue sarcoma treated with preoperative Adriamycin, radiation, and surgical excision. Although the Adriamycin postoperative adjuvant chemotherapy did not significantly benefit the experimental group relative to the control group, both groups of patients had an improved disease-free and overall survival rate compared to historical controls.

Changes in Ovarian Venous Blood Flow Following Cannulation; Effects of Luteinizing Hormone (LH) and Antihistamine

Summary The present results indicate that cannulation of the ovarian vein and subsequent hemorrhage results in rapid decline of blood flow from the cannula. This decline is significantly retarded by the administration of LH. The stimulatory effect of LH is apparently histamine-mediated, since simultaneous administration of promethazine hydrochloride completely blocks the LH-induced increase in blood flow.

Neoadjuvant Chemotherapy, Radiation, and Limited Surgery for High Grade Soft Tissue Sarcoma of the Extremity

Malignant soft tissue sarcomas of the extremity continue to present clinical challenges in terms of local tumor control and preservation of a functional extremity. Historically, surgical excision of the primary tumor was the primary mode of therapy and, in order to achieve local tumor control, radical surgical procedures were necessary.(1) This involved amputation in approximately 35% of the cases, or large compartment resections in the remainder.(2) Although these treatment methods were effective in terms of local tumor control, they all resulted in significant functional impairment. Limited surgical excision, which is possible in approximately 75% of cases, followed by high-dose radiation therapy has recently been shown to be equally effective in terms of providing local tumor control and has, in general, provided excellent function.(3–7) The goals of primary therapy in extremity soft tissue sarcomas are to obtain local tumor control, achieve the best functional results with the fewest complications, lower cost both in terms of time, money and function, and finally to design a therapy that is applicable and acceptable to the most patients.

Resection of pulmonary metastases from nonseminomatous testicular tumors: Correlation of clinical and histological features with treatment outcome

Clinical and histological correlates of survival in patients undergoing complete resection of pulmonary metastases from nonseminomatous testicular carcinoma were determined in 25 Stage C patients aged 17–38 years treated from 1969–1978. All patients had orchiectomy and retroperitoneal lymphadenectomy. Nineteen patients received combination chemotherapy before resection, and all received chemotherapy after resection. Three patients had four additional thoracotomies for pulmonary recurrence. Survival was measured from time of first thoracotomy to time of last followup or death. Actuarial survival for the entire group at one, two, and five years was 80, 63, and 59%, respectively. Median follow‐up of the survivors was 3.5 years. Patients in low tumor burden groups such as those with no tumor in retroperitoneal nodes, with unilateral metastases, or with single metastases had better prognosis, as did patients whose primary tumors were moderately well differentiated. Characteristics of pulmonary metastases that favorably influenced the prognosis were the presence of mature teratoma, presence of few mitoses, lack of mononuclear infiltrate, and lack of desmoplastic response. These findings confirm the effectiveness of multimodality therapy which includes the resection of pulmonary metastases for Stage C nonseminomatous carcinoma of the testes. In addition, they suggest that consideration should be given to the stratification of prospective clinical trials on the basis of tumor burden and histologic characteristics of the primary and metastatic lesions.