Anthony D. Nicastri

Natural History of Heroin-Associated Nephropathy

Abstract Of 14 black heroin addicts with massive proteinuria, 12 manifested a typical syndrome including edema, hypoalbuminemia and hypercholesterolemia. Renal biopsies obtained in 13 patients showed focal and segmental glomerular sclerosis in 11, typically (seven of 11 patients) associated with focal glomerular deposition of IgM and β1C/β1A globulin. Deterioration of renal function was continuous and rapid, so that in all eight patients with follow-up examinations, uremia developed in six to 48 months. Although focal sclerosis may have other as yet unidentified causes (especially in children), its occurrence in 11 of 13 nephrotic heroin addicts biopsied in the absence of other systemic or renal disease indicates a causal relation to heroin abuse. The combination of focal glomerular sclerosis and IgM and β1C/β1A globulin localization in glomeruli is otherwise unusual, having been noted in only two of 400 adult renal biopsies originating from a general nephrology service. An undefined response of the addic...

Breast self‐examination, relationship to stage of breast cancer at diagnosis

Data from 996 newly diagnosed breast cancer patients indicated a highly significant association (P < 0.001) between periodic breast self‐examination (BSE) and pathologic stage of disease. Among women reporting periodic BSE, only small differences were noted between those who practiced monthly and those who practiced several times annually. Average maximum tumor diameter and frequency of tumors 4 cm or larger were significantly greater (P < 0.01) among women who rarely or never practiced BSE. The relationship between the periodic practice of BSE and the diagnosis of breast cancer before nodal involvement was present even after controling for a wide variety of variables. The regular practice of BSE was associated with a one‐third reduction in the likelihood of diagnosis of disease with positive nodes. This difference translated to a 10% decline in five‐year mortality for whites and a 17% decline for nonwhites.

Prognostic factors in stage I carcinoma of the cervix

Abstract In a series of 177 cases of Stage I epidermoid carcinoma of the cervix, 139 were treated surgically. Increasing depth of invasion of the cervical lesion was associated with greater lateral extension and increasing vascular invasion in the cervix. Increasing depth of invasion in the cervix was significantly associated with (1) increasing incidence of pelvic node metastases, (2) increasing incidence of local extension outside the cervix with negative pelvic nodes, (3) increasing frequency of recurrence, and (4) decreasing 5-year survival. Patients with extension to the corpus and negative pelvic nodes had poor survival rates. Patients with disease confined to the cervix had poor outcome if the tumor invaded more than 10 mm and was present in vascular spaces. Poor prognostic factors to consider in therapeutic planning are (1) a depth of invasion greater than 10 mm, (2) lateral spread to more than half the cervix, (3) invasion of lymph-vascular spaces in the cervix, (4) spread to the pelvic nodes, and (5) spread to the parametria or corpus uteri.

The relationship between human papillomavirus and lower genital intraepithelial neoplasia in immunosuppressed women

In a group of 20 immunosuppressed women with lower genital neoplasia, evidence of associated human papillomaviral infection was found in all patients on the basis of the histologic identification of koilocytes in the upper strata of areas of mild or moderate dysplasia. Immunohistochemical study of similar areas disclosed human papilloma structural antigens in the lesions in 60%, while 50% had lesions in which human papilloma virions were detected by the electron microscope. An abnormal immunologic status, indicated by an altered T-helper/T-suppressor ratio, a deficient response to mitogenic stimulation, or both, was confirmed in 80% of the patients studied. Twelve of the 20 patients had unusually persistent and recurrent intraepithelial neoplasia, and in one the disorder progressed to invasive epidermoid carcinoma. The progressive behavior of human papillomavirus-associated neoplasia in these immunosuppressed patients might represent an accelerated version of the long-term course of such lesions in immunocompetent hosts.

Prognostic factors in carcinoma of the vulva

The clinical and pathologic characteristics of epidermoid carcinoma of the vulva in 84 women treated by vulvectomy were evaluated in relation to inguinal node status and survival. Tumor diameter, depth of invasion, clinical node status, vascular invasion, and pattern of invasion were all individually correlated with the pathologic status of the inguinal nodes. However, when evaluated in combination, only the clinical status of the inguinal nodes, the depth of invasion, and the pattern of invasion (in this order of significance) were predictive of pathologic inguinal node status. Tumor diameter, inguinal node status, depth of invasion, pattern of invasion, and vascular invasion were individually correlated with survival. When evaluated in combination, the clinical diameter of the lesion was the most important predictor of survival; depth of invasion and vascular invasion contributed additional information.

Incidence, significance, and follow-up of para-aortic lymph node metastases in late invasive carcinoma of the cervix

One hundred and four patients with Stages II and III of cervical carcinoma underwent para-aortic node biopsies. Of these, 12.5 per cent of patients with Stage IIA, 14.9 per cent of patients with Stage IIB, and 38.4 per cent of patients with Stage III carcinoma of the cervix had positive para-aortic nodes. They subsequently recieve 6,000 rads to the para-aortic area. The radiotherapy complication rate was high. Within four years, 50 per cent of the patients with positive para-aortic nodes had other distant metastases. The two- and four-year follow-up is presented. Only one of 13 patients with positive para-aortic nodes was alive at the end of four years.

Frequency of EGFR and KRAS mutations in lung adenocarcinomas in African Americans.

Introduction: The detection of mutations in the epidermal growth factor receptor (EGFR) gene, which predict sensitivity to treatment with EGFR tyrosine kinase inhibitors, represents a major advance in the treatment of lung adenocarcinoma. KRAS mutations confer resistance to EGFR-tyrosine kinase inhibitors. The prevalence of these mutations in African American patients has not been thoroughly investigated. Methods: We collected formalin-fixed, paraffin-embedded material from resected lung adenocarcinomas from African American patients at three institutions for DNA extraction. The frequencies of EGFR exon 19 deletions, exon 21 L858R substitutions, and KRAS mutations in tumor specimens from African American patients were compared with data in white patients (n = 476). Results: EGFR mutations were detected in 23 of the 121 specimens from African American patients (19%, 95% confidence interval [CI]: 13–27%), whereas KRAS mutations were found in 21 (17%, 95% CI: 12–25%). There was no significant difference between frequencies of EGFR mutations comparing African American and white patients, 19% versus 13% (61/476, 95% CI: 10–16%; p = 0.11). KRAS mutations were more likely among whites, 26% (125/476, 95% CI: 23–30%; p = 0.04). Conclusions: This is the largest study to date examining the frequency of mutations in lung adenocarcinomas in African Americans. Although KRAS mutations were somewhat less likely, there was no difference between the frequencies of EGFR mutations in African American patients, when compared with whites. These results suggest that all patients with advanced lung adenocarcinomas should undergo mutational analysis before initiation of therapy.

The incidence and significance of para-aortic lymph node metastases in late invasive carcinoma of the cervix

Abstract Patients with Stages IIB and III carcinoma of the cervix were subjected to laparotomy with special attention directed to para-aortic lymph nodes. Of the patients with Stage IIB carcinoma of the cervix, 16.1 per cent had metastatic disease in the para-aortic lymph nodes. Of the patients with Stage III cervical carcinoma, 46.4 per cent had positive para-aortic lymph nodes. In addition, one patient with Stage III carcinoma of the cervix had metastatic disease to the small intestine and ascending colon. Thus, 50 per cent of the patients with Stage III carcinoma of the cervix had disease beyond the usual field of radiation therapy. It is suggested that these findings demand an alteration in the concept of treatment of Stage III carcinoma of the cervix.

Vascular invasion in stage I carcinoma of the cervix

Vascular invasion was identified as an important prognostic variable for all lesion sizes in 138 patients with Stage I cervical carcinoma. A matched pairs analysis, controlling for lesion size and extracervical spread, showed that vascular invasion was significantly associated with poor outcome. Regression analysis also indicated that vascular invasion contributed prognostic information beyond that available from lesion size and extracervical spread. Studies of adjunctive therapy based on the prognostic variables are recommended. Cancer 53:1175‐1180, 1984.

Progression of Mesangial and Focal to Diffuse Lupus Nephritis

Abstract The finding of a focal glomerular lesion in systemic lupus erythematosus has been considered a good prognostic sign because the disease rarely progresses to a more severe histologic lesion and renal insufficiency. In 7.5 years, 110 of 165 such patients evaluated had clinical renal involvement, with biopsy in 69; 31 had a mesangial or focal lesion, 24 diffuse nephritis, and 14 membranous nephritis. The renal status of nine patients with an initial mesangial or focal lesion deteriorated one to 12 years later and progressed to diffuse nephritis. There was no difference between the groups with and without histologic progression in clinical severity of disease at the time of first biopsy, nor in the initial pattern of immunofluorescent or electron microscopical deposits within the glomerulus. It appears that mesangial, focal, and diffuse nephritis represent a continuum of increasingly advanced renal disease in systemic lupus erythematosus. (N Engl J Med 291:693–696, 1974)