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Background: Automated assessment of genetic abnormalities detected by fluorescence in situ hybridization (FISH) in brush cytology specimens from patients with Barrett esophagus (BE) may enhance the clinical applicability of this methodology. The objectives of this study were to validate a novel, automated, proprietary system (CytoVison SPOT AX) for the assessment of FISH abnormalities in BE brush cytology and, subsequently, to use this automated method for screening of a BE surveillance cohort., Methods: FISH with DNA probes for chromosomes 9, 17, and Y, and for the 9p21 (p16), 17q11.2 (Her2/neu), and 17p13.1 (p53) loci was applied on brush cytology specimens from a surveillance cohort of 151 patients with BE. Validation of the automated system was performed by comparison of the automated FISH results with manual scores for the first 60 patients., Results: There was 98% concordance between manual and automated FISH analysis with kappa values from 0.49 to 1 for the different probes. The loss of 17p13.1 (p53) was observed in only 5% of patients with no dysplasia (ND) and in 9% of patients with low-grade dysplasia (LGD) but increased to 46% in patients with high-grade dysplasia (HGD) (P < .005; Fisher exact test). Chromosomes 9 and 17 were observed in 6% of patients with ND, in 21% of patients with LGD, and in 62% of patients with HGD (P < .05). Ten percent of patients with ND had loss of the Y chromosome, which increased to 27% in patients with HGD (P< .05). The amplification of 17q11.2 (Her2/neu) was detected in 62% of patients with HGD (P < .001)., Conclusions: The current investigation indicated that the CytoVison SPOT AX is an objective, efficient system for the analysis of DNA-FISH on BE brush cytology and is applicable for analyzing large populations of BE patients. In the current study cohort, the loss of 17p13.1 (p53), Y chromosome loss, and polysomy of chromosomes 17 and 9 were correlated with increasing grade of dysplasia in patients with BE., ((c) 2007 American Cancer Society)

Background: Hospital mortality after esophagectomy has decreased from 29% to 7.5% over the last decades because of improved surgical techniques and better perioperative care. Suggestions have been made that a further decrease in hospital mortality may be achieved by centralization of esophagectomies in high volume centers., Methods: The effect of hospital volume on hospital mortality after esophagectomy in the Netherlands was analyzed based on data from the Dutch National Medical Registry and the Dutch Network and National Database for Pathology over the period 1993-1998., Results: Annually, approximately 310 (range, 264-321) esophagectomies are performed in the Netherlands. Fifty-two percent are performed in 43-55 low volume centers (1-10 resections a year). Six percent are performed in 1-3 medium volume centers (11-20 resections a year). The remainder (42%) is performed in two high volume centers (> 50 resections a year). Hospital mortality is 12.1%, 7.5% and 4.9% respectively (P < 0.001). The high volume centers seem to see slightly more advanced tumors than the low and medium volume centers., Conclusions: There is a significant (inverse) relation between hospital mortality and hospital volume for esophageal resection in the Netherlands. Although hospital mortality is not the only measure for quality of care, these data suggest a potential beneficial effect to centralization of esophagectomy in the Netherlands., (Copyright 2001 American Cancer Society.)

Background: As an alternative to surgical resection, endoscopic treatment modalities are being explored for the treatment of patients with early esophageal carcinoma. This study aimed to evaluate patterns of local growth and regional dissemination of early adenocarcinoma of the esophagus or esophagogastric junction, as these pathologic features may contribute to rational therapeutic decision making., Methods: Among 173 patients who underwent esophageal resection for invasive adenocarcinoma (1993-1998), 32 (19%) had early stage cancer (pT1). Clinical records, pathology reports, and original slides of the surgically resected esophagus were reviewed in each case., Results: In 12 patients tumor invasion was limited to the mucosa, whereas in 20 patients the tumor showed infiltration of the submucosa. All cancers were associated with intestinal metaplasia. Areas of high grade dysplasia accompanied 27 of the 32 cancers (84%). Intramucosal cancer had no lymph node metastasis but presented as multifocal disease in 42% of cases and extended under preexisting squamous mucosa in 17% of cases. In submucosal cancer, lymph node metastases were present in 30% of cases. Disease specific 3-year survival for patients with intramucosal cancer was 100% and for those with submucosal cancer 82% (P = not significant)., Conclusions: Based on the local growth pattern of intramucosal adenocarcinoma of the esophagus or esophagogastric junction, endoscopic treatment of patients with this disease should be applied with caution. For submucosal carcinoma, surgery is the mainstay of treatment, as lymph node metastasis is frequently present. Both subclassifications of early cancer show a favorable outcome after esophagectomy., (Copyright 2000 American Cancer Society.)

Background: The aim of this multicenter study was to investigate the feasibility and negative predictive value of sentinel lymph node detection with blue dye in vulvar carcinoma patients., Methods: In patients with squamous cell carcinoma of the vulva without suspicious groin lymph nodes, patent blue V was injected intradermally shortly before surgery. Routine groin lymph node dissection and radical vulvectomy were performed. During the surgery, blue lymph vessels and lymph nodes were identified, and the blue lymph nodes were sent separately for histologic examination. The negative predictive value of the blue lymph nodes for the absence of metastases was assessed by histologic examination of the groin lymph node specimens., Results: Fifty-one patients in whom 93 groin lymph node dissections were performed were entered. One or more blue lymph nodes were detected in only 52 groins (56%). Nine (17%) of these were tumor positive, and 6 blue lymph nodes were the only tumor positive lymph nodes in the specimen in which they were found. There were two false-negative blue lymph nodes. The negative predictive value was 0.953., Conclusions: It was shown in this multicenter study that sentinel lymph node detection in vulvar carcinoma patients with blue dye only is not feasible because its negative predictive value is too low. Further studies involving the use of a combination of radioactive labeled technetium and blue dye are warranted., (Copyright 1999 American Cancer Society.)

Background: The purpose of this analysis was to identify pathologic risk factors for recurrence and patterns of recurrence in patients with International Federation of Gynecology and Obstetrics Stage IB and IIA cervical carcinoma and negative pelvic lymph nodes after radical hysterectomy., Methods: During the period 1982-1991, 271 clinically staged patients with Stage IB or IIA cervical carcinoma underwent a Wertheim-Okabayashi radical hysterectomy with pelvic lymph node dissection. The study group was composed of 196 lymph node negative patients. Pathology slides were reviewed and multivariate analysis performed to identify independent prognostic factors., Results: The recurrence rate in the study group was 7.7%. In multivariate analysis, the following factors were identified as independent risk factors for recurrence: adenocarcinoma (P = 0.003), depth of invasion as a fraction of tumor penetration of the cervical stroma (P = 0.01), and an extensive stromal inflammatory cell infiltrate (P = 0.04). Based on these factors, the following risk groups were identified: a low risk group (N = 140, 5-year disease free interval [DFI] = 97%) and a high risk group (N = 55, 5-year DFI = 81%). An evaluation of the recurrence patterns for these patients showed a predominance of pelvic recurrences., Conclusions: This study showed that among patients with Stage IB and IIA cervical carcinoma and negative pelvic lymph nodes, a subset with a significant risk for recurrence could be identified. Because the majority of recurrences in the lymph node negative group were pelvic recurrences, the value of adjuvant radiotherapy as a treatment for selected lymph node negative patients should be evaluated in a prospective study.

Background: Patients with squamous cell carcinoma of the vulva who present with multiple positive groin lymph nodes have poor survival. Growth of cancer through the capsule of the groin lymph nodes recently has been identified as an important prognostic factor for survival in that patient group. The objective of this study was to determine the influence of several clinicopathologic parameters on the pattern of recurrence and survival., Methods: A review of 71 patients with squamous cell carcinoma of the vulva and positive lymph nodes was performed to assess the independent prognostic value of a number of variables for survival. Variables analyzed included tumor size, stage, number of positive lymph nodes, extracapsular growth of lymph node metastasis, the greatest dimension of tumor in the lymph nodes, the percentage of replacement of the lymph nodes by tumor, clinical lymph node status, and laterality of positive lymph nodes., Results: Using the Mantel-Cox test, extracapsular growth of lymph node metastases (P = 0.00), two or more positive lymph nodes (P = 0.02), and greater than 50% replacement of lymph nodes by tumor (P = 0.03) were predictors of poor survival. No difference was found between the groups with two positive lymph nodes and those with three or more. Extracapsular growth of lymph node metastases was the most significant independent predictor for survival. Distant metastases occurred in 7 of 15 patients (48%) who had a combination of extranodal spread, lymph node replacement greater than 50%, and three or more positive lymph nodes., Conclusion: Extracapsular growth of lymph node metastases in the groin is the most important predictor for poor survival in patients with squamous cell carcinoma of the vulva. Because of the predominant distant failure pattern in a subgroup of patients who have a combination of extranodal spread, multiple positive lymph nodes, and lymph nodes replaced by tumor greater than 50%, a future study of the effectiveness of systemic therapy for vulvar cancer must include these patients.

Background: The incidence of vulvar intraepithelial neoplasia Grade III (VIN III) is increasing and is diagnosed at a younger age than previously. VIN III is often multifocal and frequently coexists with multicentric dysplastic lesions in the cervix and vagina. Warty-type VIN III more often has been found to contain human papillomavirus (HPV) DNA than basaloid-type VIN III: The authors performed HPV DNA polymerase chain reaction (PCR) analysis in 48 VIN III biopsies and reverse transcriptase (RT)-PCR in 8 HPV-16 DNA-positive multifocal VIN III biopsies to detect E6/E7 transcripts., Methods: Human papillomavirus DNA detection and histologic analysis were performed on alternating slides of paraffin embedded biopsies. Polymerase chain reaction was performed with consensus primers, and HPV typing was performed by direct sequencing. Total RNA was isolated from frozen biopsies by centrifuging a guanidinium thiocyanate (GTC) lysate through a cesium chloride (CsCl) cushion. The RT reaction was performed using a 3' primer, located just downstream of the E7 stop codon, and the PCR reaction was performed using the same 3' primer and a 5' primer located just downstream of the E6 start codon., Results: The mean age of the 48 patients was 37.7 years. Eighty-one percent had multifocal VIN III: Sixty-six percent had multicentric neoplasia. Forty-six percent of the biopsies were warty-type, 17% basaloid-type, 35% mixed-type and 2% differentiated-type. Ninety-two percent were HPV-positive and 83% contained HPV-16 DNA. Human papillomavirus DNA was more often present in multifocal VIN III lesions than in unifocal VIN III lesions and also more often in VIN III lesions coexisting with other dysplastic multicentric lesions than in unicentric VIN III lesions. Warty-type VIN III more often contained koilocytes than basaloid-type VIN III: A correlation between different morphologic forms of VIN III and the presence of HPV DNA was not found. Both types of VIN III often coexist in one lesion. In all the RT-PCRs, a 593-base-pair fragment was detected, corresponding to the expected length of the major E6*-E7 mRNA., Conclusions: The observed high prevalence of transcriptionally active HPV DNA associated with multifocal and multicentric dysplasia suggests a role of HPV in the pathogenesis of these lesions. A positive correlation between different morphologic forms of VIN III and the presence of HPV DNA was not found.

Between January 1, 1983, and December 31, 1988, operations were performed on 112 patients with adenocarcinoma of the gastric cardia. Resection of the primary tumor was performed in 93 patients. For these 93 patients, follow-up until July 1, 1989, averaged 24 months, during which time 59 patients died. Positive resection margins carried a greater risk for the development of a local recurrence but did not correlate with survival. The cumulative overall 5-year actuarial recurrence rate was 69%. The cumulative 5-year recurrence rate for metastases was 64% and for locoregional recurrence it was 36%. The overall 5-year survival rate was 24%. Differences in survival were observed between patients with carcinomas of the various subgroups of the 1987 TNM classification system (T1-T2 versus T3-T4, N0 versus N1-N2, M0 versus M1, Stages I-II versus Stages III-IV, Grades 1-2 versus Grades 3-4). In particular, lymph node status as correlated with histopathologic grade showed remarkable differences in survival: patients with no positive lymph nodes in the resection specimen and a Grade 1 or 2 tumor had a significantly better 5-year survival rate (53%) than the other subgroups (N0/Grades 3-4: 21%; N1-N2/Grades 1-2: 12%; N1-N2/Grades 3-4: 14%).

A case of nonseminomatous testicular cancer and enlarged mediastinal lymph nodes, which were interpreted as metastases, is reported. When there was no change after two courses of chemotherapy, a mediastinoscopy was performed and the results showed sarcoidosis.