Surgery has witnessed few procedures that have been so rapidly adopted into clinical practice as sentinel node biopsy (SLNB) in patients with breast carcinoma. Critics note that sentinel node biopsy has been not validated by any randomized clinical trials that are the customary sine qua non for the adoption of innovations in medicine; advocates maintain that, as a diagnostic procedure, it does not require the same lengthy, randomized trials that the adoption of a new treatment mandates, and that its accuracy has already been validated by studies comparing SLNB with traditional axillary dissection in the same patient(s). Which of these positions is more correct is moot, since SLNB has been adopted ubiquitously by surgical specialists around the world, and current major concerns relate to perfecting its use.Sentinel node biopsy for breast carcinoma was introduced in the mid-1990s, and it has now been performed on thousands of patients with breast carcinoma (men as well as women); nevertheless, there remains a myriad of unanswered questions. Controversy abounds concerning patient selection criteria, surgical technique and complications, handling of the sentinel node(s) by the surgical pathologist, adjuvant therapy for axillary node "sub-micrometastasis" detected only by immunohistochemistry, and other details of the procedure, as well as safety for patients and personnel.To address these various issues, an international consensus conference was convened in Philadelphia, Pennsylvania, April 19-22, 2001. The conference included individuals representing the disciplines of surgical oncology, surgical pathology, breast imaging (radiology), nuclear medicine, radiation oncology, and medical oncology, each of them highly experienced in this new technique.The group attempted to reach consensus on the following issues: 2542
BACKGROUND. A number of conventional histopathologic features have been associated with recurrence of ductal carcinoma in situ (DCIS) after surgery alone and are included in the Van Nuys Pathologic Classification and Prognostic Index. To the authors' knowledge, very little is known regarding the prognostic significance of the many biologic markers that have been studied in DCIS in the past decade. METHODS. Clinical and pathologic data were analyzed from 151 patients who underwent wide local excision alone for DCIS that was diagnosed by mammography or as an incidental finding between 1982 and 2000. Using local disease recurrence as an endpoint, the authors sought to determine the prognostic significance of a large number of histopathologic parameters as well as biologic markers (estrogen receptor [ER], progesterone receptor [PR], p53, HER-2/neu, Ki-67, p21, and bcl-2), as determined by immunohistochemical staining of contemporary or archival tissue. RESULTS. With a median follow-up of 65 months, 42 recurrences were reported to occur between 11 months and 97 months after definitive surgery. In a univariate analysis, tumor size, Van Nuys pathologic classification, and degree of necrosis demonstrated significant correlations with the rate of recurrence. Tumor size, necrosis, nuclear grade, and comedonecrosis were found to be associated significantly with the time to disease recurrence. None of the biologic markers demonstrated a significant association with the rate of recurrence or the time to disease recurrence. In a multivariate analysis, only large tumor size (Van Nuys 2 or 3) and higher degrees of necrosis (Van Nuys 2 or 3) were found to be associated significantly with both the rate of recurrence and the time to recurrence. No biologic marker showed a significant correlation with recurrence. Using Classification and Regression-Tree Analysis and Tree-Structured Survival Analysis, PR Ͼ 3.5% and bcl-2 Ͻ 97.5% were associated with a higher recurrence rate in the subgroup of patients with small tumor size (Van Nuys size 1) and higher degrees of tumor necrosis (Van Nuys 2 or 3). CONCLUSIONS. The current results confirmed the value of conventional histopathologic parameters, as outlined in the Van Nuys classification system, in predicting local recurrence of DCIS. Using traditional logistic analyses, no significant correlation was found between a variety of biologic markers and disease recurrence.
Twelve patients developed herpes simplex (HSV) hepatitis a median of 18 days after solid organ transplantation. This is earlier than cytomegalovirus hepatitis, which usually occurs 30-40 days after transplantation. Eight recipients (67%) died, and in seven, the diagnosis was made at autopsy or <48 h before death. Clinical manifestations associated with mortality were hypotension, disseminated intravascular coagulation (DIC), metabolic acidosis, gastrointestinal bleeding, and bacteremia. Laboratory abnormalities at diagnosis associated with mortality were high creatinine, low platelet counts, prolonged partial thromboplastin time, and a high percentage of band forms on the blood smear. Disseminated HSV disease was noted in four of six patients who had an autopsy and included involvement of lungs in three and the gastrointestinal tract in three. Five recipients developed DIC and all died. Pathologically, HSV hepatitis has two forms, focal and diffuse. All three patients with diffuse liver pathology died. However, three of seven with focal liver pathology survived with antiviral therapy, which suggests that early diagnosis and treatment may be lifesaving. None of these patients had received prophylactic acyclovir. It is possible that acyclovir prophylaxis may be able to prevent this disease.Herpes simplex virus (HSV) hepatitis is considered rare [1]. It has been observed most frequently as part of disseminated HSV in immunologically compromised patients or during pregnancy. Sporadic cases have been reported from this institution in renal transplant recipients and have ended fatally [2,3], as have most cases reported in the literature. Here we report 12 cases that occurred after solid organ transplantation over a 9-year period (1980)(1981)(1982)(1983)(1984)(1985)(1986)(1987)(1988). This series is large enough to allow us to determine the approximate frequency of HSV hepatitis in our transplantation population; to present the effect of viral dissemination, the nature of the liver pathology, and the range of clinical and laboratory characteristics of the disease; and to investigate prognostic factors. Materials and Methods DefinitionsCases of HSV hepatitis were diagnosed by laboratory, histologic, and clinical findings of one or more of the following in liver tissue from a biopsy or autopsy: isolation of HSV, positive immunoperoxidase staining for HSV antigen, or histology showing intranuclear inclusion bodies and pathology consistent with HSV lesions. In one case there was no liver tissue to examine, and the diagnosis was made by isolation of HSV from multiple sites outside the liver, including buffy coat, and clinical evidence of fulminant hepatitis. The histologic pattern of Laboratory methodsTissue specimens obtained by biopsy or at autopsy were examined after routine staining and processing for detection of HSV antigen by immunoperoxidase staining and, on occasion, processed for isolation of HSV. Other specimens obtained from transplant recipients for viral isolation included throat wash, urine, buffy co...
We used a murine monoclonal antibody to herpes simplex virus (HSV) type 2 (HSV-2) glycoprotein G (gG) to develop an enzyme immunoassay that detected HSV-2 type-specific antibodies in human sera. Antibodies to HSV-2 gG were detected in 98 (96%) of 102 sera from pregnant women with culture-proved HSV-2 infection. Sixty-five percent of the women had serological evidence of past HSV-2 infection by the Rawls index, based on titers of neutralizing antibody to HSV type 1 and HSV-2. Thirty (88%) of 34 infants exposed to maternal HSV infection at delivery had antibodies to HSV-2 gG and remained well. One infant exposed to primary maternal HSV-2 infection lacked antibodies to HSV-2 gG and developed neonatal HSV-2 infection. The mean +/- SD optical density by HSV-2 gG enzyme-linked immunosorbent assay for sera obtained from 17 infants within one week after onset of neonatal HSV-2 infection was 0.25 +/- 0.12, compared with 1.15 +/- 0.34 in cord blood sera from exposed infants who did not develop symptoms (P less than .0001 by t test).
BACKGROUND The aim of this study was to compare the outcomes of bilateral breast carcinoma (BBC) patients with those of patients who had unilateral disease. METHODS From 1960 to 1995, 1465 Stage 0–III patients with primary breast carcinoma were treated with either mastectomy or breast conservation therapy at the Kimmel Cancer Center of Jefferson Medical College and Thomas Jefferson University Hospital. There were 1315 (89.9%) unilateral, 103 (7.1%) metachronous, and 47 (3.0%) synchronous breast carcinoma patients. Patients with synchronous breast carcinoma were defined as having a contralateral cancer diagnosed within 1 year of initial diagnosis. The percentage of patients with Stage 0–I disease at initial diagnosis was 49.4%, whereas 68% had Stage 0–I disease at subsequent diagnosis. For patients with metachronous breast carcinomas, the median interval between the first and second diagnosis was 44 months (range, 13–287 months). The median follow‐up time was 58 months (range, 12–229 months) for patients with synchronous cancers and 87 months (range, 0.25–414 months) for those with metachronous cancers. Rates of overall survival and survival with no evidence of disease (NED survival), local control, and distant metastasis from the time of the second diagnosis were calculated for patients with synchronous and metachronous disease. These figures were then compared with each other and also with those for unilateral breast carcinoma patients. RESULTS Patients with synchronous and metachronous breast carcinoma had worse 5‐ and 8‐year NED survival rates compared with unilateral breast carcinoma patients, as well as an increased risk of distant metastasis. In multivariate analysis, differences in local control and overall survival were not statistically significant for patients who had bilateral disease compared with those who had unilateral disease. There was no difference when patients with metachronous and unilateral breast carcinoma were compared with respect to local control and overall survival. CONCLUSIONS Patients with bilateral breast carcinoma who present with synchronous disease are at greater risk for distant metastasis than women with unilateral or metachronous breast tumors. There was a trend toward decreased overall survival and local control for patients with synchronous bilateral breast carcinoma compared with patients who had either metachronous or unilateral disease. Cancer 2000;88:2739–2750. © 2000 American Cancer Society.
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