Is frozen section analysis of reexcision lumpectomy margins worthwhile? Margin analysis in breast reexcisions.

BACKGROUND: The authors performed reexcision lumpectomy on patients with breast cancer with tumor at or close to the resection margin or if the margin status was unknown. Frozen section analysis (FSA) of reexcision lumpectomy margins was performed to allow additional excision of margins or mastectomy, saving the patient another operation or an additional radiation boost. METHODS: The authors reviewed the accuracy of FSA of margins in 107 patients undergoing reexcision lumpectomy between 1987 and 1992. There were 359 frozen sections performed on 156 specimens. Sensitivity and specificity of FSA for each frozen section margin, specimen, and patient were evaluated, as was gross inspection of tumor involvement at the resection margins. The accuracy of each pathologist's use of FSA also was evaluated. RESULTS: FSA sensitivity per frozen section margin, specimen, and patient was 0.90, 0.89, and 0.85, respectively. The specificity of gross inspection was 0.97, 0.96, and 0.96 (sensitivity, 0.44), which was significantly less accurate than that of FSA (P = 0.0015) or permanent section (P = 0.019). There was no significant discordance between FSA and permanent section. Of 19 pathologists doing FSA, 6 evaluated 10 or more specimens. The error rate ranged from 4% to 10% among pathologists with 10 or more readings, whereas 12 of 13 pathologists with fewer readings had no errors. The final pathologist had a 100% error rate, significantly worse (range, P = 0.0085-0.02) than any experienced pathologist. Thirty-four (32%) patients underwent additional excision (24 patients) or mastectomy (10 patients) based on the results of FSA, which saved the patients from undergoing another operation. No one required an additional operation or a mastectomy because of a false FSA result. CONCLUSION: FSA is safe and accurate in evaluating reexcision lumpectomy margins. Gross inspection is not reliable in margin evaluation. FSA saved an additional operation 32% of the time. Obtaining clear margins during one procedure eliminates the necessity of an additional radiation boost and probably will improve cosmesis.

Neoadjuvant chemoradiation in pancreatic and duodenal carcinoma. A Phase II Study.

BACKGROUND: Low resectability rate and high locoregional recurrence are major factors contributing to the failure of surgical treatment for localized pancreatic adenocarcinoma. A Phase II study involving preoperative 5-fluorouracil (5-FU) and mitomycin C and radiation therapy was evaluated. METHODS: Thirty-one patients with biopsy-proven carcinoma (24, head of pancreas; 2, body; 5 duodenum) were treated with preoperative radiation therapy, 5040 cGy (180 cGy/fraction, 5 days/week), concurrent with 5-FU, 1000 mg/m2/day continuous infusion (days 2-5, 28-32) and mitomycin C 10 mg/m2 bolus (day 2). Ten patients had previous laparotomy or bypass surgery and were deemed unresectable; 21 had percutaneous, endoscopic retrograde choleangiopancreatic, or transhepatic stent biopsies. RESULTS: Toxicity included neutropenic fever (2 patients), biliary sepsis (2 patients), and nausea and vomiting requiring total parenteral nutrition. One patient died of biliary sepsis before completion of chemoradiation and 11 patients showed evidence of metastatic disease (clinical or occult). Resectability rate was 38% (10/26) for pancreatic carcinoma and 80% (4/5) for duodenal carcinoma. Pathology of the resected specimens revealed extensive necrosis and hyalinization with clear margins in all cases. Lymph node metastases were found in one case of pancreatic carcinoma. The four resected duodenal carcinomas contained no residual tumor in the specimens. At a median follow-up of 29 months, the median survival time for those with pancreatic carcinoma was not yet reached in the resection group and was 8 months in the nonresection group. The corresponding actuarial 5-year survival rates were 58% and 0%, respectively. CONCLUSIONS: Neoadjuvant chemoradiation therapy was given safely to patients with pancreatic and duodenal carcinoma. It facilitated complete resection in 38% of patients with pancreatic carcinoma and 80% of those with duodenal carcinoma. A significant downstaging of positive margins and regional lymph nodes occurs as a result of preoperative chemoradiation.

Heterotopic mucinous cystadenoma of the pancreas.

A 46-year-old female who had been experiencing severe diarrhea and marked weight loss underwent exploratory laparotomy because of a mass near the tail of the pancreas noted on CT scan. Pathologic examination revealed a mucinous cystadenoma of the pancreas occurring in heterotopic pancreatic tissue. This is the second reported case of mucinous cystadenoma occurring in heterotopic pancreatic tissue.

Intrathoracic organ injury associated with photodynamic therapy.

Photodynamic therapy has been proposed as a new modality for the local treatment of neoplasms limited to the pleural surface. Clinical use of photodynamic therapy will involve exposure of large surface areas of normal intrathoracic organs to tumoricidal doses of photodynamic therapy. This study details the pathologic changes that occur within the lung, heart, trachea, and diaphragm of Sprague-Dawley rats after administration of tumoricidal photodynamic therapy. Animals were injected with the photosensitizer Photofrin-II (Quadralogic Technologies, Vancouver, B.C., Canada), 10 mg/kg intraperitoneally, 24 hours before surface illumination of a portion of the target organ with gold vapor laser light (628 nm) (124 joules/cm2). Control animals were treated with light alone. After endotracheal intubation and mechanical ventilation, the lung and heart were exposed via left thoracotomy. The trachea was dissected in the neck, and the diaphragm was visualized via celiotomy. One site was treated per animal. Animals were killed at 24 hours, 48 hours, 72 hours, 1 week, 1 months, and 6 months after therapy. Histologic injury was numerically assessed by a single observer blinded to treatment and time of organ harvest. The Wilcoxon matched-pair signed-rank test was used to determine the statistical significance of differences between treated and control groups. Twenty-four hours after treatment the lung, heart, and trachea of rats subjected to photodynamic therapy demonstrated parenchymal injury (p less than 0.05). The diaphragm showed delayed injury 72 hours after therapy (p less than 0.05). Microscopic pulmonary changes included alveolar and endothelial disruption, intraalveolar hemorrhage, and fibrin deposition. Coagulation necrosis of myocardial fibers extending through the epicardium to involve up to 50% of myocardial thickness was observed. The diaphragm showed mesothelial hyperplasia with necrosis of superficial skeletal muscle. No similar gross or microscopic changes were present in the organs of control animals, or more than 48 hours after treatment in the trachea of animals that received photodynamic therapy. Photodynamic therapy induces a spectrum of tissue-specific injury, which may affect its usefulness in subsequent clinical trials.

Microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation.

An analysis was performed of 39 consecutive women with microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation during the period 1977 to 1988. Microinvasive ductal carcinoma was defined as predominantly intraductal carcinoma with microscopic or early invasion. Surgical treatment of the primary tumor included excisional biopsy or wide resection. Axillary lymph node staging showed that 37 patients were pathologically node negative and two patients were pathologically node positive, each with only one positive lymph node. The median follow-up was 55 months (mean = 65 months; range = 25-135 months). The 5-year actuarial rate of overall and cause-specific survival were both 97%. The 5-year actuarial rate of freedom from distant metastases was 93%. Nine patients developed a recurrence in the breast; eight of the nine patients had isolated local only first failures, and one of the nine patients had a local recurrence simultaneously with distant metastases. The median time to local failure was 42 months (mean = 53 months; range = 20-116 months). Of the eight patients with local only first failure, seven patients have been salvaged with further treatment and remain free of disease at the time of last follow-up, and one patient has died of subsequent distant metastatic disease. Median follow-up after salvage treatment was 29 months (mean = 27 months; range = 0-54 months). Comparison of the patients with microinvasive ductal carcinoma with two control groups of intraductal carcinoma and invasive ductal carcinoma was performed. Although the rate of local failure was significantly higher for patients with microinvasive ductal carcinoma as compared to the two control groups, the rates of survival and freedom from distant metastases for patients with microinvasive ductal carcinoma were intermediate to the two control groups. Because of the high rates of survival and freedom from distant metastases and because of the ability to salvage patients with local recurrence, breast-conserving surgery and definitive irradiation should continue to be considered as an alternative to mastectomy for appropriately selected and staged patients with microinvasive ductal carcinoma of the breast.

Definitive irradiation for intraductal carcinoma of the breast.

During the period from 1978 to 1985, 51 women with intraductal carcinoma of the breast were treated with definitive irradiation following breast-conserving surgery. Surgical treatment of the primary tumor in all patients consisted of excisional biopsy or wide resection. In general, definitive irradiation consisted of conventional breast tangents to 4500-5000 cGy followed by a breast boost to a total dose of 6000-6600 cGy (median = 6000 cGy; range = 4200-6600 cGy). No patient was treated with radiation to a supraclavicular or axillary field. For the 51 patients, the median follow-up was 68 months (range = 25-126 months). The 5-year actuarial rate of local failure was 6%. A total of five patients failed in the breast at 19, 35, 40, 79, and 119 months following definitive irradiation. Salvage treatment in these five patients consisted of mastectomy in all five patients plus adjuvant tamoxifen in one patient. All five of the patients with breast failures are alive and NED (no evidence of disease), although with limited follow-up (median = 12 months; range = 6-68 months). These results suggest that definitive irradiation is an acceptable alternative to conventional mastectomy for appropriately selected and staged patients with intraductal carcinoma of the breast. In view of the long natural history of this disease, prolonged and careful follow-up of these patients is required.

Increased resectability of locally advanced pancreatic and periampullary carcinoma with neoadjuvant chemoradiotherapy.

A prospective neoadjuvant trial utilizing chemotherapy (CTX) and radiotherapy (XRT) prior to pancreatectomy was established to determine the feasibility of resection after aggressive pretreatment and its effect on survival. Fifteen patients with pancreatic cancer (14 head, 1 body) and 1 patient with duodenal cancer, (with paraaortic adenopathy), were subjected to combination treatment with infusional 5-FU, bolus injection of mitomycin-C, and XRT (4 patients were treated off the protocol). Patients were restaged 3 wk after XRT, and those deemed resectable underwent a pancreatic resection. Three patients did not undergo exploration after the neoadjuvant therapy, although two of these were deemed resectable by CT scan. The remaining 13 patients underwent exploration and 10 underwent resection. Three did not undergo resection because of extrapancreatic disease, although their primary tumors were resectable. One patient had no residual tumor in the specimen. The others had residual tumor with evidence of necrosis and hyalinization, but all margins were free of tumor. There were two perioperative deaths from sepsis. Of the remaining patients who underwent resection, one died of a myocardial infarction at 9 mo. One patient died with recurrent disease at 19 mo. The remaining patients are alive 40, 32, 11, 11, 10, and 4 mo since diagnosis and are currently free of disease. Aggressive neoadjuvant chemoradiotherapy can be performed safely, allows successful resection, and may yield long-term survival or curve.