Treatment of advanced head and neck cancer with concomitant radiation and chemotherapy.

Forty-four patients with predominantly inoperable or recurrent head and neck cancers were treated with combined chemotherapy (CT) and radiation therapy (RT) in a Phase I/II study. CT and RT were combined in a concomitant fashion to take advantage of radiosensitizing properties of the chemotherapeutic agents. Each treatment cycle consisted of cisplatin 60 mg/M2 on day 1, 5-FU infusion at a dose of 800 mg/M2 per day continuously for 5 days and RT at 200 cGy per day, days 1 through 5. The treatment cycle was repeated every 2 weeks for 7 cycles in patients treated curatively and for 2 to 6 cycles in patients treated palliatively due to prior radiation therapy or the presence of metastatic disease. Regional control was achieved in 98% of the patients. Regional control has persisted in 87% of the patients treated curatively with a minimum follow-up of 24 months. Distant failure occurred in 23% of this group. Actuarial survival of 2 years for the curative group is 66%. Concomitant combination of radiation with radiation potentiating chemotherapeutic agents shows promise of increase in local control.

Should multicentric disease be an absolute contraindication to the use of breast-conserving therapy?

PURPOSE: Multicentric cancer is present in a large proportion of mastectomies performed as treatment of breast cancer; it has been considered a contraindication to breast conservation. METHODS AND MATERIALS: We reviewed the records of our patients with Stage I or II breast cancer treated with breast conserving surgery and radiation therapy over a 13-year period. Twenty-seven patients had two or more nodules of grossly visible cancer separated by histologically normal breast tissue. All patients had grossly negative margins of excision; however, four patients had microscopically positive margins. Nine patients had positive axillary nodes. All patients received radiation therapy to the breast postoperatively, with a median dose of 50.4 Gy in 28 fractions; 11 patients also received a boost dose of 6-20 Gy to the tumor bed. Eleven patients were given adjuvant chemotherapy and one patient was given adjuvant tamoxifen. RESULTS: With a median follow-up of 53 months, only one patient has relapsed in the breast (3.7%); that patient relapsed in multiple distant sites at the same time. Three patients have died of disseminated disease; the actuarial survival and disease-free survival rates at 4 years are 89%. CONCLUSION: Breast conservation may be considered for patients with multicentric breast cancer discovered at the time of histologic examination. For patients with multicentric disease detected prior to surgery, breast conserving therapy may be appropriate as long as: (1) all clinically and radiographically apparent abnormalities are removed, (2) clear margins of resection are achieved, and (3) there is no extensive intraductal component.

Adenocarcinoma in Barrett's esophagus.

The association of adenocarcinoma with Barrett's esophagus stimulated a review of our experience to study the clinical presentation, pathology, and results of management. Nineteen patients (15 men and four women) satisfied the criteria of primary adenocarcinoma arising in columnar epithelium in the esophagus. The majority had dysphagia (95%) and weight loss (63%). Nearly three fourths of the patients also had a history of hiatus hernia or esophagitis. Diagnosis was confirmed preoperatively in all by endoscopic biopsy and/or cytologic study. Potentially curative resection was performed in 15 patients and palliative procedures in four. Fourteen patients had advanced (Stage III) disease and only five had Stage I or II disease. Multicentric disease within the esophagus was found in seven patients. Postoperative complications included empyema, hemothorax, and pneumonia (one case each). The only postoperative death resulted from complications of previously undetected brain metastases. The median survival of the 15 patients having resection for cure is 12 months. Four are alive, one with disease at 46 months and three free of disease at 19, 87, and 93 months. All four patients undergoing palliative procedures died within 8 months. The study demonstrates that multifocal presentation of the tumor is common in this group of patients and that long-term survival is possible when early tumors are managed aggressively.

Synchronous, metachronous, and multiple hepatic resections of liver tumors originating from primary gastric tumors.

BACKGROUND: The role of hepatic resection for noncolorectal gastrointestinal malignancies involving the liver is not well defined. To address this issue we studied our experience with resection of liver tumors arising from primary gastric malignancies. METHODS: A retrospective study of 195 patients who underwent a total of 207 liver resections identified 12 patients with primary gastric cancer who underwent 16 resections for liver involvement. There were 10 adenocarcinomas and two leiomyosarcomas. We examined the type of hepatic surgery, the status of residual disease, and the primary histologic findings. Morbidity, mortality, and actual survival rates were recorded. RESULTS: Thirty-day operative mortality was 8.3% (1 of 12). Hospital mortality was 25% (3 of 12). Operative morbidity occurred in three of nine survivors (33%). Synchronous en bloc resection (n = 3) of stomach and liver for adenocarcinoma produced two long-term survivors (no evidence of disease for 10 and 13 years). Mean survival after synchronous discontinuous resection (n = 4) was 8 months (range, 2 to 17 months). Metachronous resection for adenocarcinoma (n = 3) produced one long-term survivor (74 months), and one patient with recurrent leiomyosarcoma underwent a total of five liver resections and survived 64 months. CONCLUSIONS: For adenocarcinoma, en bloc resection of contiguous liver involvement produced long-term survivors. Synchronous resection of discontinuous metastases did not. Metachronous resection of isolated disease and multiple resections of recurrent isolated disease may have value in carefully selected patients.

Pulmonary resection for metastatic breast cancer.

Thirty-three patients treated primarily with surgical excision of pulmonary metastases from breast cancer were compared with 30 patients treated primarily with systemic chemohormonal therapy. Treatment for patients in the surgical group included pulmonary resection alone in 20, resection plus adjuvant systemic therapy in nine, and resection plus adjuvant radiation therapy in four. Treatment for patients in the medical group included systemic therapy alone in 22 and systemic therapy plus local radiation therapy in eight. Mean survival in the surgical group was significantly longer than that in the medical group, even when only those patients who manifested single pulmonary nodules were compared (58 months vs 34 months). The overall 5-year survival rate after treatment of lung metastasis was significantly greater for the surgical group than for the medical group (36% vs 11%). The results of this study indicate that surgical resection should be considered in patients with breast cancer who develop operable pulmonary metastases without evidence for concomitant extrapulmonary disease. In selected patients, such therapy may result in a survival benefit.

The dilemma of delayed cellulitis after breast conservation therapy.

OBJECTIVE: To determine the clinicopathologic characteristics of patients with breast cancers in whom delayed breast cellulitis developed after conservation therapy (lumpectomy, axillary dissection, and radiation). BACKGROUND: Breast cellulitis developing after conservation therapy represents a difficult diagnostic and management dilemma because determination of its origin may be necessary before further treatment decisions can be made. METHODS: In this retrospective evaluation of 184 sequential patients with breast cancers who underwent conservation therapy, 10 study patients (5%) in whom breast cellulitis developed 3 or more months after surgery were compared with the 174 patients in whom cellulitis did not develop. RESULTS: There was no significant difference in clinicopathologic characteristics of the study patients compared with control patients. The cellulitis resolved in 5 patients (50%) and persisted from 4 months to more than 1 year in 5 patients (50%). The cellulitis recurred in 1 patient who responded to repeated therapy. The 5 patients with persistent cellulitis underwent biopsies, and recurrent cancer was found in 1 patient. Recurrent cancer did not develop in the patients whose cellulitis resolved within 4 months with a minimum follow-up of 24 months. CONCLUSIONS: Delayed-onset cellulitis occurs in a small percentage of patients with breast cancers treated by conservation therapy. The cellulitis may take several weeks to clear, and/or it may recur or persist. If the condition persists after 4 months of therapy, a biopsy should be performed to rule out recurrent cancer.

The adrenal medullary transplant operation for Parkinson's disease: clinical observations in five patients.

The recent report by Madrazo and coworkers on the successful treatment of Parkinson's disease using adrenal medullary tissue transplanted to the caudate nucleus has aroused international interest in the procedure. The present article reports our initial experiences with the operation in five patients and discusses the postoperative effects of the procedure, the protocol used to monitor motor performance, and the need for cooperation with the two registries that have been created to follow morbidity, mortality, and efficacy. We intend to alert the neurosurgeon to important side effects, but not to assess the long term efficacy of the procedure. Postoperatively, a number of transient effects were seen in our patients, the most striking being somnolence, delusions, and lack of significant pain in spite of a large abdominal incision. The only complications have been respiratory. After the early postoperative period, gradual improvement of on-off times and Schwab-England disability scores was seen over 20 weeks. Long term cooperative studies are needed to demonstrate the efficacy of this procedure. neurosurgeons doing transplant operations are urged to join the registries so that uniform information can be collected.

Juvenile nasopharyngeal angiofibroma. A 30 year clinical review.

Thirty-one patients with juvenile nasopharyngeal angiofibroma treated at Memorial Sloan-Kettering Cancer Center from 1949 to 1979 were reviewed. Eighteen of the patients were previously untreated and in the other 13, previous treatment elsewhere had failed. Median follow-up was 54 months. All the patients were male adolescents whose presentations were characterized by epistaxis (73 percent) and nasal obstruction (60 percent). The tumors invariably arose within the nasal cavity or nasopharynx and involved neighboring structures in 58 percent of the patients. Treatment included surgery (30 patients), radiotherapy (13 patients), the administration of androgens (11 patients), sclerotherapy (2 patients), and cryotherapy (1 patient). Of the 18 primary patients, 14 were managed surgically with irradication of disease in 12 (86 percent). Of the four primary patients initially treated nonsurgically, disease recurred in three, all of whom were rendered free of disease by surgical excision. Of the 13 secondary patients, 8 were free of disease after surgery only, and 2 were free of disease after multimodal therapy with surgery being the last treatment employed. There were no deaths. Maxillary radionecrosis (one patient) and facial cellulitis (three patients) constituted the only significant morbidity. This study has demonstrated the clinical characteristics of juvenile nasopharyngeal angiofibroma and supports the primary role of surgical excision in its management.

Major chest wall resection for recurrent breast carcinoma.

Local recurrence of breast cancer is a relatively common entity. Occasionally, the management of such recurrences necessitates full-thickness chest wall resection. Although the chance for cure in such circumstances is small, achieving local control remains a desirable goal to maintain comfort and hygiene. This study evaluates the utility and morbidity of full-thickness chest wall resection in the control of symptomatic local recurrence of breast carcinoma. Twelve patients, undergoing such resections, were identified from hospital records. The resections included an average of three ribs (range, two to five) and, in seven cases, part or all of the sternum. A variety of rigid and soft tissue chest wall reconstructive techniques were utilized. Of the 11 patients available for follow-up, ten reported good overall function postoperatively. There were no postoperative deaths and only one patient developed a major complication requiring prolonged hospital stay. The patients spent an average of 6.6 hours in surgery, 14.6 hours intubated, and 20 days in the hospital. There were ten patients available for long-term follow-up. At the time of this study, 70 per cent were still alive, with or without disease, with a mean survival of 27 months (range, 3-71 months). Forty per cent were alive, disease-free, with a mean survival of 36 months (range, 3-71 months). This series demonstrates low morbidity, improved quality of life, and the possibility of long-term, disease-free survival after full-thickness chest wall resection for recurrent breast carcinoma.

Malignant cystosarcoma phyllodes.

UNLABELLED: This study reviewed 26 women who had resection of a malignant cystosarcoma phyllodes. Clinical presentations were palpable mass, 25; pain, 11; and ulceration, 2. Definitive surgical therapy was radical mastectomy (RM), 2; modified radical mastectomy (MRM), 14; total mastectomy (TM), 4; and partial mastectomy (PM), 6. Tumors ranged in size from 1-20 cm (median, 7 cm). Eight patients developed recurrent disease after 10-45 months. Local recurrence was more likely after TM and PM than after MRM and RM (P < 0.05). Patients who developed local recurrence only were treated by wide re-excision, and all such patients are alive with no evidence of disease at 5-25 years. Only one of 16 patients undergoing axillary dissection had involved lymph nodes. Four patients whose tumors ranged from 5-8 cm and who underwent one RM and three MRM developed systemic recurrence; all died of their disease after 15-48 months. CONCLUSION: 1) Although there is a higher local recurrence after PM and TM as compared with MRM and RM for malignant cystosarcoma phyllodes, the local recurrence can be treated with wide excision without affecting long-term survival; 2) systemic recurrence was not related to size or extent of resection; 3) axillary dissection does not predict for or prevent recurrence.

Impaired cholesterol esterification in the plasma in patients with breast cancer.

An important factor which determines the movement of cholesterol in and out of the cells is the free cholesterol (FC)/esterified cholesterol (EC) ratio in the plasma. Although this ratio has been shown to be increased in several types of malignancies in humans as well as experimental animals, it is not known whether such an abnormality is found in breast cancer patients. Furthermore, the reasons for such an increase in cancer patients are unknown. We studied the plasma lipid composition and the activity of lecithin-cholesterol acyltransferase (LCAT), the enzyme responsible for the formation of most of EC in human plasma, in 12 women with breast cancer and 9 age-matched control women. The plasma EC concentration was found to be significantly decreased in cancer patients, whereas the FC concentration was unchanged, leading to increased FC/EC ratios (P < 0.05). The concentration of phosphatidylcholine, the acyl donor in the LCAT reaction, was decreased significantly, whereas all other phospholipids were unaffected. The cholesterol-esterifying activity of LCAT was significantly lower in cancer patients, whether assayed with endogenous substrates (P < 0.05), or with an exogenous substrate (P < 0.01). However, another function of the enzyme, namely the lysolecithin acyltransferase activity, was increased (P < 0.02), indicating that the enzyme concentration in plasma may not be decreased. These results show that the increase in the FC/EC ratio in cancer patients is due to an impaired esterification of cholesterol by plasma LCAT, probably due to an alteration in the composition of substrate lipoproteins, or the presence of an inhibitory factor.

The use of a ketamine-propofol combination during monitored anesthesia care.

UNLABELLED: Supplemental analgesics are commonly used to enhance analgesia and improve patient comfort during procedures performed under local anesthesia and sedation. Because the use of ketamine as an analgesic adjunct to propofol sedation has not been well established, we evaluated its impact on analgesia, sedation, and recovery after ambulatory surgery. One hundred female outpatients undergoing breast biopsy procedures under local anesthesia participated in this randomized, double-blinded, placebo-controlled study. After premedication with midazolam, 2 mg IV, patients received an infusion of a solution containing propofol (9.4 mg/mL) in combination with either placebo (saline) (Group 1) or ketamine, 0.94 mg/mL (Group 2), 1.88 mg/mL (Group 3), or 2.83 mg/mL (Group 4). The sedative infusion rate was varied to maintain a deep level of sedation (Observer Assessment of Alertness/Sedation score 4) and normal respiratory and hemodynamic functions. Sufentanil, 2.5 microg IV, "rescue" boluses were used as needed to treat patients' responses (if any) to local anesthetic infiltration or surgical stimulation. Ketamine produced a dose-dependent reduction in the "rescue" opioid requirements. However, there was an increase in postoperative nausea and vomiting, psychomimetic side effects, and delay in discharge times with the largest ketamine dosage (Group 4). The adjunctive use of ketamine during propofol sedation provides significant analgesia and minimizes the need for supplemental opioids. The combination of propofol (9.4 mg/mL)/ketamine (0.94-1.88 mg/mL) provides effective sedation/analgesia during monitored anesthesia care. IMPLICATIONS: Ketamine, when used in subhypnotic dosages, may be an useful adjuvant to propofol sedation.

Synchronous, bilateral mastectomy.

Sixty-four patients (mean age, 51 years) had mastectomies which were synchronous and bilateral. Sixty-one premastectomy biopsies (bilateral, 34 and unilateral, 27) demonstrated the following: invasive carcinoma, 17; noninvasive carcinoma, 24; combination of above, 10; and benign disease, 10. Twenty-two patients had bilateral mastectomy because of bilateral positive biopsy. Twenty-nine patients with unilateral carcinoma on biopsy had bilateral mastectomy. Thirteen patients had bilateral mastectomy despite benign disease only on biopsy (10) or no biopsy (3). Ten unexpected carcinomas (34%) were found in the contralateral breast in the 29 patients with carcinoma diagnosed on unilateral biopsy. The biopsy pathology of these 10 specimens was invasive ductal carcinoma in 1 and multifocal, noninvasive carcinoma (ductal, 3 and lobular, 6) in 9. An unexpected carcinoma may be found in the contralateral breast in a significant number of patients who are selected for bilateral mastectomy, particularly if the selection is on the basis of a noninvasive, lobular histology. Bilateral mastectomy may be appropriate for such patients, particularly when complicated by a strong family history and breasts which are difficult to assess by physical or mammographic examination.

Hormone receptor studies in axillary metastases from occult breast cancers.

The authors describe 11 patients with occult breast carcinoma, who initially presented with axillary nodal metastases of unknown origin. In all 11 cases, physical examination and mammography results were normal. Steroid hormone receptor studies were done on tissue from all 11 axillary masses and 2 masses underwent lactalbumin staining as well. In 8 of the 11 patients these studies were positive, suggesting breast as the primary tumor site. Estrogen (30 to 445 fmol/g) or progesterone (30 to 1059 fmol/g) receptors, or both, were positive in seven cases. Although a breast carcinoma was subsequently found in all 11 patients, receptor studies on the primary tumor could not be done in every instance. The authors concluded that performing steroid hormone receptor assays on axillary metastases from occult tumors not only may provide information regarding the identity of the primary tumor but also may be the sole opportunity to determine its hormone receptor status.

The role of ultrasonography in the evaluation of primary hyperparathyroidism.

Ultrasonography was used preoperatively in 21 patients with primary hyperparathyroidism in an effort to locate enlarged parathyroid glands. It indicated the presence of a solitary mass compatible with a parathyroid adenoma in 14 patients. At operation, adenomas were found at the location indicated by ultrasonography in 13 of the 14 patients (93 per cent). In seven patients, ultrasonography failed to reveal evidence of a mass of the parathyroid gland. At operation, three had diffuse parathyroid hyperplasia and four had a solitary adenoma. Of the four patients with adenomas undetected by ultrasonography, one patient had an adenoma which had undergone infarction and three had coexisting nodular thyroid gland disease. We concluded that ultrasonography is valuable in the preoperative assessment of patients with primary hyperparathyroidism. This is especially so in the absence of coexisting nodular thyroid gland disease. When positive, ultrasonography accurately locates adenomas, and when negative, it strongly suggests the presence of hyperplasia. This may have clinical application in limiting the extent of dissection and, thereby, reducing the morbidity of parathyroid gland exploration.

Carcinoma of the breast: detection with MR imaging versus xeromammography.

Detectability of breast cancer with magnetic resonance (MR) imaging versus xeromammography was quantitatively compared. MR images were obtained of breasts of 120 women who underwent xeromammography. T1 values were determined for masses larger than 2 cm. Cancer was histologically confirmed in 39 breasts and was considered excluded from 81 due to results of biopsy, cyst aspiration, or sonography or absence of change in xeromammographic findings over time. Images were blindly interpreted by three observers, and results were expressed as receiver operating characteristic curves. Detectability of breast cancer was substantially better with xeromammography than with MR imaging for all observers (P less than .03, 10(-6), and .001). On MR images, spiculation of a mass, distorted architecture, skin thickening, and nipple or skin retraction were specific but relatively insensitive indicators of cancer. Masses with smooth, distinct margins and signal intensity greater than that of fat on T2-weighted images were always benign. Other findings and T1 values were not diagnostically useful. The authors conclude that xeromammography is superior to MR imaging in detection of breast cancer.