Melanoma thickness and histology predict sentinel lymph node status.

BACKGROUND: It remains unclear which patients with melanoma will benefit most from lymphatic mapping and sentinel lymphadenectomy. The purpose of this study is to determine whether primary melanoma histopathologic features could be applied to predict sentinel node status. METHODS: One hundred twelve patients underwent sentinel node biopsy between May 1995 and August 1999. Reported histologic features were assessed for predictive value by univariate and multivariate logistic regression. RESULTS: The sentinel node was located successfully in 105 of the 112 patients (94%). Twenty-one of these 105 patients (20%) had sentinel nodes that were positive for metastatic disease. Multivariate analyses revealed that tumor thickness greater than 1.5 mm (P = 0.01), ulceration (P <0.01), and lymphovascular invasion (P = 0.05) predicted the presence of micrometastases. CONCLUSIONS: The presence of unfavorable histopathology such as ulceration and lymphovascular invasion may identify a group of patients with thin melanomas who would benefit from sentinel lymphadenectomy.

The effect of tamoxifen and cisplatin on the disease-free and overall survival of patients with high risk malignant melanoma.

The adjuvant treatment of high-risk malignant melanoma remains problematic. Previously we reported moderate success in the treatment of metastatic disease using tamoxifen, cisplatin, dacarbazine and carmustine. Based upon data that suggested tamoxifen and cisplatin were the active agents in this regimen, we initiated a phase II trial of this combination in the adjuvant setting. We treated 153 patients with 4 cycles of tamoxifen (160 mg day(-1), days 1-7) and cisplatin (100 mg m(-2), day 2) for 28-day intervals. Patients received an anti-nausea regimen of dexamethasone with ondansetron or granisetron. During the first 2 years of follow-up, patients were evaluated every 2 months with a history, physical exam, laboratory work and computed tomography scans of the chest, abdomen and pelvis every 4 months. Thereafter, patients were evaluated every 3 months and radiographic studies were performed if necessary. Currently, with a median follow-up of 36 months, the disease-free survival (DFS) is 68.4% and overall survival (OS) is 84.5%. Kaplan-Meier analysis predicts a 5-year DFS of 62% with an OS of 79%. Relapses after 20 months have been rare. No effect of gender or number of positive lymph nodes was noted, however, stage of disease prior treatment was a factor. The major toxicity proved to be gastrointestinal in nature with nausea the most prevalent symptom. Minimal renal, haematologic and neurologic toxicity occurred. These preliminary results suggest that there is a positive impact of tamoxifen and cisplatin on both the DFS and OS of high-risk malignant melanoma patients. The 5-year projected DFS and OS compare favourably with those reported for the ECOG 1684 trial and warrant confirmation in a prospective randomized trial.

A pilot study evaluating the efficacy of a fully acetylated poly-N-acetyl glucosamine membrane formulation as a topical hemostatic agent.

BACKGROUND: Topical hemostatic agents are frequently needed for control of intraoperative bleeding. Currently available topical products each have potential drawbacks, making a more effective topical hemostatic agent desirable. This study was performed to evaluate the effectiveness of a particular formulation of a newly available polysaccharide polymer, poly-N-acetyl glucosamine (p-GlcNAc), as a topical hemostatic agent for use in the operating room. Swine splenic incision and splenic capsular stripping hemorrhage models were initially used, with a subsequent pilot human study then performed. METHODS: For the swine splenic incision model, anesthetized immature female Yorkshire white swine had a 3 x 8 mm incision created on the spleen. One of 3 agents (p-GlcNAc membrane, oxidized cellulose, or absorbable collagen) was sequentially applied to individual wounds and digitally compressed for 20 seconds. The wound was observed without pressure for 2 minutes. Up to 8 wounds per animal were created in 7 animals. For the swine splenic capsular stripping model a 2 x 2 cm area of capsular stripping on the surface of the spleen to a depth of 3 mm was created. Either p-GlcNAc membrane or oxidized cellulose was applied and digitally compressed for 60 seconds, followed by observation without pressure for 2 minutes. Six wounds per animal were created in 2 animals. If bleeding persisted in either model, a new cycle of compression was applied. These steps were repeated until hemostasis was achieved. No change in hemodynamics or coagulation factors was observed in either model. Subsequently, 10 consecutive patients undergoing elective small-bowel surgery were enrolled on pilot study. A 5 x 3 x 3 mm cruciate incision was created midway between the mesenteric and antimesenteric borders of the small bowel. Either p-GlcNAc membrane formulation or oxidized cellulose was applied (the sequence alternated per patient) with a 400-mg weight used for even, direct pressure. A second cruciate incision was then created on the contralateral side of the bowel to evaluate the second material. The number of applications required for hemostasis was assessed. Hemodynamics, small-bowel pathologic condition, and hematologic parameters were evaluated. RESULTS: The p-GlcNAc membrane required fewer cycles of compression in the swine splenic incision model to achieve hemostasis than either absorbable collagen or oxidized cellulose (1.25 vs 2.58 and 3.41, respectively; P < .01) and caused more effective immediate cessation of bleeding (79% for p-GlcNAc vs 17% for both absorbable collagen and oxidized cellulose). With the more traumatic splenic capsular stripping model, p-GlcNAc required fewer cycles of compression to achieve hemostasis than oxidized cellulose (average, 2.5 versus 6.8 respectively; P < .01) and was able to achieve hemostasis with greater efficacy (50%) in 2 applications than did oxidized cellulose (0%; P < .01). When used in the human pilot study, p-GlcNAc membranes required fewer cycles of compression than oxidized cellulose (2.5 vs 5.4, respectively; P < .002), was able to stop bleeding with greater efficacy in 1 cycle of compression (50% vs 0%, respectively; P < .01), and ultimately accomplished hemostasis in 80% of the cases as opposed to 20%. CONCLUSIONS: On the basis of its greater hemostatic efficacy as compared with collagen or oxidized cellulose-based products, p-GlcNAc holds promise as an effective topical hemostatic agent and deserves further evaluation.

Detection of occult breast cancer micrometastases in axillary lymph nodes using a multimarker reverse transcriptase-polymerase chain reaction panel.

BACKGROUND: Axillary lymph node status in breast cancer patients remains the single most important predictor of outcomes. Current methods of histopathologic analysis may be inadequate because 30% of node-negative patients recur. The purpose of this study was to test the hypothesis that a multigene reverse transcriptase-polymerase chain reaction (RT-PCR) panel provides a more sensitive method to detect axillary lymph node metastases than routine pathologic examination. STUDY DESIGN: Sixty-one consecutive breast cancer patients were evaluated, with nine normal control patients. Nodes > 1 cm were bisected for histopathologic and RT-PCR analysis. Nodal tissue was homogenized, and total RNA was converted into cDNA with reverse transcriptase. Reverse transcriptase-polymerase chain reaction analysis was performed with primers specific for keratin-19, c-myc, prolactin inducible protein (PIP), and beta-actin using ethidium bromide gel electrophoresis. Reverse transcriptase-polymerase chain reaction positive/ pathology negative axillary lymph nodes were reevaluated using step sectioning and immunohistochemical staining. RESULTS: Thirty-seven patients had pathologically negative axillary lymph nodes, of which 15 (40%) were positive by RT-PCR analysis. Two RT-PCR negative results (one probably from tissue processing error and the other secondary to sampling error) among the 24 histologically positive specimens were detected (8%). The number of patients in each pathologic stage was 26 patients in stage I; 18, stage IIA; 7, stage IIB; 7, stage IIIA; 3, stage IIIB; and 0 patients in stage IV. By RT-PCR staging, 8 of 26 patients went from stage I to IIA (30%), and 7 of 18 from stage IIA to IIB (39%). Of the RT-PCR positive individuals who were stage I by pathologic analysis, 100% were found to be c-myc positive, 0% keratin-19 positive, and 0% PIP positive; for stage IIIB patients these markers were 50%, 100%, and 100% respectively. Additionally, an increasing number of positive markers per specimen appeared to correlate with larger primary tumor size (p < 0.01) and decreased predicted 5-year survival (r = 0.950, p < 0.002). CONCLUSIONS: Multimarker RT-PCR analysis appears to be a readily available and highly sensitive method for the detection of axillary lymph node micrometastases. Longterm followup of RT-PCR positive patients will be required to determine its clinical relevance. If validated as a predictor of disease recurrence, this method would provide a powerful complement to routine histopathologic analysis of axillary lymph nodes.

Efficacy of reverse transcriptase-polymerase chain reaction screening for micrometastic disease in axillary lymph nodes of breast cancer patients.

Pathologic examination of axillary lymph nodes (ALNs) may miss micrometastases in 30 per cent of breast cancer patients. We have developed a multimarker reverse transcriptase-polymerase chain reaction (RT-PCR)-based screening method that detects histopathologically positive ALNs with a 5 per cent false-negative rate. The purpose of this study was to compare this RT-PCR methodology with histopathology with regard to sensitivity and cost. Pathologically negative ALNs from 35 breast cancer patients were re-evaluated by a single pathologist in a blinded fashion using serial sectioning with immunohistochemical staining. Histopathologic results were then compared with those of RT-PCR. Cost analysis was performed based on standard charges for these methods. RT-PCR identified micrometastases in 14 of 35 pathologically negative nodes. Serial sectioning and immunohistochemical staining identified micrometastases in two cases, with RT-PCR positive for one of these. The charge per specimen for performing routine histopathologic examination was $380, serial sectioning and immunohistochemical staining $787, and RT-PCR $125. RT-PCR appears to be more sensitive at detecting ALN micrometastasis than histopathologic examination even with serial sectioning and immunohistochemical staining. If micrometastatic breast cancer detected by RT-PCR proves to be clinically relevant, it could be a more effective screening methodology with significant cost savings as compared to currently available pathologic examinations.

Stereotactic core biopsy of the breast: results of one-year follow-up of 101 patients.

Stereotactic core biopsy (SCB) is being used as a cost-effective alternative to needle localized biopsy (NLB). However, an area of concern is the potential for sampling error, with sparse surgical data available concerning follow-up and failure rates. We therefore reviewed our results in patients undergoing SCB for mammographically detected breast abnormalities. Between January 1994 and February 1995, 128 patients underwent SCB. Average age was 56.4 years. Nine patients (7.0%) had histologic evidence of malignancy, with 111 (86.7%) benign diagnoses requiring no further initial intervention. Eight patients (6.3%) proceeded directly to NLB, five because of technical failure of SCB and three because of suspicious initial histology. One of the latter patients had ductal carcinoma in situ. The remaining 111 SCB patients were evaluated at 6 months and 1 year by mammographic and physical examination. Ten patients were lost to follow-up. Of the remaining 101 patients, 98 (97%) had stable mammograms and normal physical examinations. Three patients (3.9%) required subsequent NLB due to progression of the mammographic lesion. Two cases were histologically benign, and 1 patient had ductal carcinoma in situ adjacent to the previous SCB biopsy site. An additional patient underwent NLB for a new radiographic abnormality at a separate location in the ipsilateral breast, which was invasive ductal carcinoma. SCB appears to be an effective alternative to NLB for the majority of patients deemed eligible. Careful mammographic follow-up is warranted for these patients given the small, but real, possibility of sampling error.

Combined modality therapy in the treatment of epidermoid carcinoma of the anus at the Medical University of South Carolina.

Treatment of anal epidermoid carcinoma by radiation and chemotherapy does offer an excellent opportunity to maintain quality of life. No patient in this series suffered long-term complications; and all have maintained rectal, anal, and sexual function. Patients with early stage lesions (AJC I-II) are most amenable to anus conserving therapy for epidermoid cancer of the anus. The success rate is markedly diminished in patients having more advanced disease, with patients possessing AJC stage III and VI disease presenting major problems. The possibility of post operative radiation therapy is markedly compromised by preoperative radiation therapy. Clinical surveillance and early recognition of these lesions by primary physicians can now offer patients with lesser stage cancer of this type excellent opportunity for organ preservation therapy. For those patients presenting with Stage III and VI carcinoma of the anus the aforementioned problems should be addressed and discussed before initiating conservative therapy.

Breast cancer screening in a biracial community: the Charleston tricounty experience.

Breast cancer remains a major cause of death among women in South Carolina. Mammography, breast self-examination, and clinical breast examination are effective methods for early detection and subsequent mortality reduction. The Tricounty Breast Cancer Screening Survey assessed knowledge of these methods and recommendations among 503 women in the Charleston area. While 57% of all respondents reported performing breast self-examination at least once per month, 13% of blacks and 6% of whites reported that they do not know how to perform the procedure. Clinical breast examinations within the past year were reported by 69%, yet 11% of blacks and 4% of whites reported that they had never had the examination. More than one third (40%) of all 503 women reported ever having had a mammogram, and 22% reported having had one within the past year. However, 18% of the blacks and 5% of whites reported never having heard of the procedure. The major barriers to mammography appear to be the belief that women do not need regular mammograms and the lack of recommendations by their physicians. Survey results support the need for educating women about what the procedures are, the importance of using them regularly, and the means to comply with them.

Radiation enteritis.

As the population receiving radiation therapy grows, so does the incidence of chronic radiation enteritis. A review of the pathology of chronic radiation enteritis reveals fibrosis, endarteritis, edema, fragility, perforation, and partial obstruction. Conservative management of patients with this disease is common. Because the obstruction is only partial, decompression is easily achieved with nasogastric suction and parenteral support. The patient is then often discharged on a liquid-to-soft diet. This therapeutic strategy does nothing for the underlying pathology. The problem, sooner or later, will return with the patient further depleted by the chronic radiation enteritis. We think surgical intervention is appropriate when the diagnosis of chronic radiation enteritis is assumed. The surgery in relation to this disease is high risk with a 30% mortality and 100% expensive morbidity. Early intervention seems to decrease these figures. All anastomoses, if possible, should be outside the irradiated area. Trapped pelvic loops of intestine should be left in place and a bypass procedure with decompressing enterostomies accomplished. The surgery should be performed by a surgeon with extensive experience with all kinds of bowel obstruction as well as experience in performing surgery in radiated tissue.

Lobular carcinoma in situ of the breast.

Lobular carcinoma in situ of the breast is a well defined pathologic entity which is found in about 2.5 per cent of all specimens of the breast taken for biopsy and most commonly occurs in premenopausal females. Its diagnosis is virtually always incidental due to the absence of any clinical indication of its presence. This lesion carries a significant risk for development of subsequent invasive carcinoma which applies equally to both breasts and which appears to increase with time. The appropriate treatment of this disease remains a controversial issue. Various aspects of its epidemiology, pathology and natural history which have an important bearing on the therapeutic decision as well as the many treatment options available are analyzed herein. There is certainly a perception that lobular carcinoma in situ represent the early form of a malignant process which can be cured or prevented if appropriately treated at this stage. At the very least, an understanding of this lesion holds the potential for broadening our understanding of the physiologic basis of carcinoma of the breast as a whole.

Analysis of pancreatoduodenectomy.

Between 1956 and 1982, there were 55 pancreatoduodenectomies performed at the Medical University of South Carolina by 19 different surgeons. There were 26 resections for adenocarcinoma of the head of the pancreas and 16 resections for carcinoma of the ampulla of vater, carcinoma of the extrahepatic biliary ducts, and carcinoma of the duodenum. There were seven resections for chronic pancreatitis. There were two resections for trauma and three resections in the (1960s) for carcinoma of the stomach. There was one resection for cystadenocarcinoma of the pancreas. In the patients with carcinoma of the pancreas, resection was only performed when there was no gross evidence of extension beyond the parenchyma of the pancreas. Analysis of the resected specimen revealed 44% of the pancreatic carcinomas subsequently had positive lymph nodes. None of these patients became long-term survivors. Failure of the pancreato-jejunostomy was the most serious complication, occurring in 7 of 55 resections. There were no fistulas where a mucosal to mucosal anastomosis was performed to join the pancreas with the jejunum. The five-year survival for all patients with carcinoma of the pancreas was 11.6%. The 3 five-year survivors were from resections performed between 1956 and 1970. During these years, the mortality rate for the procedure was 21%. From 1970 to 1982 there were no five-year survivors from carcinoma of the pancreas. However, the mortality rate was 10.6%. The history and current controversies over this surgical procedure are reviewed.

Radiofrequency thermotherapy, local chemotherapy, and arterial occlusion in the treatment of nonresectable cancer.

Localized radiofrequency thermotherapy (RFTT) has been effective by itself in debulking cancers but has not accomplished total eradication by itself. Occlusion of the regional artery supplying the tumor drastically reduces the arterial pressure distal to occlusion and further impairs tumor blood flow leading to an accentuation of the temperature differentiation achieved by the normal tissue and tumor. Radiofrequency thermotherapy with vascular occlusion is combined with direct injection of an effective chemotherapeutic agent into the tumor. Radiofrequency thermotherapy is performed after injection of chemotherapy using bleomycin and mitomycin C for squamous cell cancers and Adriamycin and mitomycin C for adenocarcinoma. There are no adverse systemic responses to the small dose of chemotherapy used and the combination therapy is effective in destroying the tumor.

Another cause of nipple discharge. Mammary duct ectasia with periductal mastitis.

Mammary duct ectasia with periductal mastitis is a distinct, benign form of breast pathology that is different from fibrocystic disease of the breast. There are no known increased risk factors for developing breast cancer from this entity. The treatment is local surgical excision which relieves symptoms and does not significantly alter the appearance of the breast.