Favorable Histologic Findings Research Articles

Wilms Tumor

Wilms Tumor

Synchronous bilateral Wilm's tumor with complete radiographic response managed without surgical resection: a report from the National Wilm's Tumor Study 4

Purpose We reviewed the long-term local tumor control in patients with bilateral Wilm's tumor (BWT) who received no definitive surgical therapy to one kidney after complete radiographic resolution after initial chemotherapy. Methods National Wilm's Tumor Study 4 (NWTS-4) enrolled 3335 patients (pts) during the period August 1986 to August 1994. There were 188 pts with BWT or 5.6% of the total enrolled. The treatment records and imaging reports were reviewed to ascertain those children who had documented tumors without definitive surgical therapy after initial treatment. Patients who did not have renal surgery because of progression of tumor were excluded from this study. Results Eleven children had no definitive surgical treatment of renal lesions in one kidney (right, 6; left, 5) after initial treatment with chemotherapy and/or radiation therapy. The pretreatment size of the lesions were less than 3 cm (4 pts), 3 to 6 cm (5 pts), more than 6 cm (1 pt), and unknown (1 pt). Prechemotherapy biopsy was performed in 6 of 11 patients. Lesions were less than 3 cm (1 pt), 3 to 6 cm (3 pts), more than 6 cm (1 pt), and unknown (1 pt). Four biopsy specimens showed favorable Wilm's histologic findings. One lesion (4 cm) showed an intralobar nephrogenic rest, another lesion of unknown size was read as favorable histologic findings vs perilobar nephrogenic rest. Biopsy was not performed on 5 lesions (4 pts, <1 cm; 1 pt, 3cm). Only 2 children in this study received radiation treatment. One child received 1050 cGy whole abdominal radiation, and 1 child received 1060 cGy to the left flank postnephrectomy. Radiation therapy was not given to any patient because of failure of the tumor to respond to chemotherapy. Five patients received treatment regimen EE-4A, dactinomycin, and vincristine. The duration of therapy ranged from 24 to 102 weeks for an average of 55.6 weeks. Three patients received treatment regimen DD-4A, dactinomycin, vincristine, and doxorubicin for 28, 52, and 52 weeks, respectively. Three patients received 2 separate regimens of chemotherapy. One child was treated with dactinomycin, vincristine, and cyclophosphamide for 60 weeks and then received regimen EE-4A for 24 weeks. Another patient received regimen EE-4A for 16 weeks and then regimen DD4-A for 36 weeks. One child received regimen EE-4-A for 12 weeks and then regimen DD4A for 40 weeks. Management of the contralateral kidney was complete nephrectomy in all 11 patients. There were no local relapses in the renal tumor bed. All patients were alive at a median follow-up of 9 years (range, 9 months to 15 years). Conclusion Children with synchronous BWT or Wilm's tumor and contralateral nephrogenic rests that have radiographic resolution, after initial treatment, have a low risk for local relapse. These children should be followed by serial imaging.

Ureteral extension in Wilms' tumor: a report from the National Wilms' Tumor Study Group (NWTSG)

Background Extension of Wilms' tumor into the ureter is a rare event. We reviewed the National Wilms' Tumor Study Group (NWTSG) database to define the clinical presentation, associated pathologic features, and clinical outcome of these patients. Methods Records of children identified to have ureteral extension of Wilms' tumor enrolled in NWTS-3, 4, and 5 were reviewed. Presenting symptoms, diagnostic studies, histopathologic findings, operation performed, and outcome were recorded. The NWTS-5 surgical data were prospectively collected as part of the quality assurance program. Results Forty-five children were identified with ureteral extension. For NWTS-5, the incidence of ureteral extension was 2%. Clinical presentations were gross hematuria in 22 patients, 2 had passage of tissue per urethra, and 1 child had a urethral mass. The remainder had nonspecific presentations. Ureteral extension was seen on preoperative imaging in 14 patients, intraoperatively in 22, and on pathologic examination in 9 patients. Hydronephrosis was noted in 12 patients, and there was nonfunction of the kidney in another 8. Laterality of the tumor was right side in 26 and left in 19. Cystoscopy was performed in 12 children. Findings included tumor seen at the ureteral orifice in 6 patients and bleeding from the orifice in one child. All patients had radical nephrectomy including partial ureterectomy. The ureteral margin was positive in 3 patients, including 2 of the 7 with separate removal of the ureteral extension. The number of patients in each clinical stage was as follows: stage I, 10; stage II, 18; stage III, 14; and stage IV, 3. The tumor extended into the proximal ureter in 23 patients, distal ureter in 13, 7 had extension into the bladder, and 1 had urethral involvement. The level of ureteral extension was not clearly noted in the 45th child. The median follow-up was 96 months. Overall, 41 of 45 patients were alive at last contact. There were 3 deaths because of tumor in patients with unfavorable histologic tumors, and 1 because of treatment toxicity in a child with favorable histologic findings. Conclusions Ureteral extension occurs in approximately 2% of patients with Wilms' tumor. The diagnosis should be suspected in patients with gross hematuria, hydronephrosis, or nonfunctioning kidney. Cystoscopy with retrograde ureterogram may aid in preoperative diagnosis in these patients. Preoperative diagnosis is important because complete resection of the involved portion of ureter at the time of nephrectomy can avoid residual disease and the need for second surgery or radiation therapy.

Prospective histologic evaluation of intra-abdominal prosthetics four months after implantation in a rabbit model

Placement of an intraperitoneal prosthetic is required for laparoscopic ventral hernia repair. The biocompatibility of these prosthetics determines the host's inflammatory response, scar plate formation, tissue ingrowth, and subsequent mesh performance, including prosthetic compliance and prevention of hernia recurrence. We evaluated the host response to intraperitoneal placement of several prosthetics currently used in clinical practice. A 4-cm x 4-cm piece of mesh was implanted on intact peritoneum in New Zealand white rabbits. The mesh types included expanded polytetrafluoroethylene (ePTFE) (DualMesh), ePTFE and polypropylene (Composix, heavyweight polypropylene), polypropylene and oxidized regenerated cellulose (Proceed, midweight polypropylene), and polypropylene (Marlex, heavyweight polypropylene). At four months, standard hematoxylin and eosin and Milligan's trichrome stains of the mesh-tissue interaction were analyzed by three observers blinded to the mesh types. Each specimen was evaluated for scar plate formation, inflammatory response, and tissue ingrowth. Each of these three categories was graded on a standard scale of 1-4 (1 = normal tissue and 4 = severe inflammatory response). The scores were analyzed using Wilcoxon rank sum test with p < 0.05 as significant. Ten samples of each mesh type were evaluated. There was no difference in tissue incorporation between the groups. The mean scar plate formation was greater in the heavyweight polypropylene meshes than for DualMesh (p = 0.04). With Proceed, the reduction in scar plate formation compared with that for Composix and Marlex approached statistical significance (p = 0.07). The mean number of inflammatory cells was greater around the ePTFE when compared with the midweight polypropylene (p = 0.02) but equal to the other meshes. The four prosthetic materials evaluated in this study demonstrate comparable host biocompatibility as evidenced by the tissue ingrowth. Scar plate formation around DualMesh was significantly less than that around Composix and Marlex. Interestingly, more inflammatory cells were noted surrounding the DualMesh which was equal to that of the heavyweight meshes. Proceed, a midweight polypropylene mesh, has the potential for improved patient tolerance compared to heavyweight polypropylene meshes based on its favorable histologic findings.

Dr. Gary J. Becker Young Investigator Award: Comparison of Small-Diameter Type 1 Collagen Stent-Grafts and PTFE Stent-Grafts in a Canine Model—Work in Progress

To report an in-progress experiment in a canine model in which two types of small-diameter stent-grafts-one constructed of polytetrafluoroethylene (PTFE) and the other of a new, type 1 collagen material-were compared regarding vessel patency, intimal hyperplasia formation, and tissue reaction. Six mongrel dogs weighing 30-35 kg were used. Stent-grafts of 4-mm diameter and 20-mm length were constructed with use of balloon-expandable stainless-steel stents wrapped with either PTFE or a new type 1 collagen graft. Stent-grafts were placed in deep femoral arteries bilaterally (PTFE on one side, collagen on the other). Animals were followed for 2 weeks (n = 2), 6 weeks (n = 2), or 12 weeks (n = 2). Percent stenosis based on angiographic findings as well as thickness and area of neointimal hyperplasia were compared at each time point and compared with use of the Student t test. All devices were patent in the immediate postimplantation period. Five of six collagen stent-grafts and five of six PTFE implants were patent at follow-up. In-stent stenosis was undetectable angiographically in all five patent collagen stent-grafts. All five patent PTFE stent-grafts showed demonstrable in-stent stenosis (10%-60%), indicating a trend toward improved patency in collagen stent-grafts versus PTFE stent-grafts (P = .07). Neointimal hyperplasia was absent at 2 weeks in the collagen stent-grafts. Neointimal thickness increased to a maximum of 360 microm at 12 weeks in the collagen stent-grafts. For PTFE stent-grafts, neointimal hyperplasia was present in all samples and reached a maximum of 770 microm at 12 weeks (P = .03). Even in small-diameter vessels, type 1 collagen stent-grafts demonstrate excellent patency rates and favorable histologic findings. The type 1 collagen stent-graft technology merits further developmental efforts in preclinical models.

Favorable Histologic Findings and Tensile Strength at 14 Years in Knitted Polyester Aortofemoral and Femoropopliteal Grafts in the Same Patient

Patent right and left limbs of an aortobifemoral knitted polyester graft and a patent left femoropopliteal graft, both implanted for 14 years, were removed 40 hr postmortem from a 63-year-old man. Healing studies were performed, using routine and immunocytochemistry staining scanning electron microscopy (SEM), and transmission electron microscopy (TEM) on multiple samples taken from sites sufficiently far from the anastomoses to avoid pannus healing. Evaluation by weight-elongation comparison with a fresh graft demonstrated that structural stability and strength were well preserved. Anastomoses were patent with no remarkable intimal hyperplasia. There was no thrombus on the flow surface of either graft. Histologic studies of these grafts revealed uniform through-wall tissue ingrowth and extensive patches of endothelial cells scattered over the flow surface, confirmed by factor VIII, SEM, and TEM. These findings document that long-term stable tensile strength and healing with flow surface endothelialization can be attained with knitted polyester grafts in the human.

Race and clinical outcome in endometrial carcinoma

Objective: To compare the outcomes of black and white women who have surgically staged endometrial carcinoma. Methods: We retrospectively compared the clinicopathologic factors, socioeconomic status, treatments, and outcomes of 70 black and 302 white women who were treated for surgically staged endometrial carcinoma at our institution. Results: Black women had higher-grade tumors, less favorable histologic findings, more comorbid illnesses, and lower socioeconomic indices. A nonsignificant trend was also seen toward more advanced-stage disease. The extent of surgical staging and types of adjuvant therapies were similar. On univariate analysis, black women had worse 5-year disease-free survival than white women (52.8% versus 75.2%; P = .001). Other significant factors included stage, grade, lymph node status, extension to the uterine serosa, cervical involvement, histology, adnexal involvement, lymphovascular invasion, myometrial invasion, positive peritoneal cytology, level of education, and household income. After controlling for pathologic and socioeconomic differences in multivariate analysis, race remained a significant prognostic factor ( P = .008; hazard rate 2.0; 95% confidence interval 1.2, 3.5). Conclusion: In a large cohort of surgically staged and uniformly treated patients with endometrial carcinoma, black race was associated with significantly worse outcomes, even after controlling for clinicopathologic and socioeconomic factors.

Nuclear morphometric analysis of metastasis in Wilms' tumor after multimodal therapy: Comparison with primary tumor

Objectives. The outlook for children with Wilms' tumor has improved with the use of multimodal therapy, and survival rates now exceed 85%. Yet, 15% of children with tumors with favorable histologic findings continue to recur unpredictably. We previously reported that nuclear morphometry (the distribution of nuclear roundness factor [NRF], lowest values for ellipticity, and age) when combined in a multivariate analysis accurately predicted response to therapy for patients with histologically favorable Wilms' tumors. Methods. To investigate further the nuclear shape changes associated with disease recurrence, we analyzed histologic sections taken from primary tumors and postmultimodal therapy metastatic lesions for 7 children who had a recurrence with initially histologically favorable primary tumors. Results. Mean NRF was significantly lower ( P = 0.0001) in the metastatic lesion (35 ± 5) group when compared with the primary tumor group (50 ± 5). The percent coefficient of variation for NRF was also significantly lower ( P = 0.006) in the metastatic lesion when compared with the primary tumor. Nuclear area was increased ( P = 0.02), although the nuclear perimeter was unchanged ( P = 0.1). Conclusions. (1) Nuclei in metastatic lesions from Wilms' tumors with favorable histologic findings after multimodal therapy are more round and exhibit less variable distribution, suggesting clonal homogeneity within the metastatic lesion. (2) Nuclei in the metastatic lesions have greater area than in the primary tumors yet have an unchanged perimeter, which may be due to internal nuclear expansion secondary to increased cellular deoxyribonucleic acid (DNA) ploidy. Although the results of this study are promising, we are currently extending this hypothesis in a larger group of patients.

Response rates in relapsed wilms' tumor. A need for new effective agents

Three hundred eighty-one children with Wilms' tumor were treated in the United Kingdom Children's Cancer Study Group WT1 Study (1982 to 1986). Seventy-one patients had relapses during or after treatment with surgery and chemotherapy, and radiation therapy, depending on stage and histologic characteristics. Forty-nine patients were evaluable for disease response to second-line chemotherapy alone. Evaluation of response to chemotherapy was impossible in the remaining patients because either surgery or radiation therapy was used at the time of relapse. With second-line combination chemotherapy (which included ifosfamide, etoposide/VM26, cisplatin/carboplatin, bleomycin, melphalan, and Thiotepa [Lederle Laboratories, Pearl River, NY]), there were five complete responses and 12 partial responses. In patients with favorable histologic findings, six of nine with Stage I, five of ten with Stage II, none of 11 with Stage III, three of 16 with Stage IV, and one of five with Stage V disease survived. Two survivors were treated with chemotherapy alone; the others received combined treatment with chemotherapy, radiation therapy, and/or surgery. For those with unfavorable histologic findings of any stage, only two of 20 survived. The authors conclude that, even for patients with localized disease with favorable histologic findings, the "salvage" rate is little more than 50%, and for all other stages and histologic findings the likelihood of cure after relapse is remote. There is clearly a need for additional effective chemotherapeutic agents for these patients.

Intracardiac extension of Wilms' tumor. A report of the National Wilms' Tumor Study.

Extension of Wilms' tumor through the inferior vena cava into the heart presents a formidable clinical challenge. Excision of such a tumor without provoking emobilization may require cardiopulmonary bypass (CPB). The completeness of excision and the likelihood of tumor embolization during operation guide subsequent radiation therapy (RT) and chemotherapy. To help define these issues, the clinical records of 15 patients enrolled in three National Wilms' Tumor Studies (NWTS) who had intracardiac tumor extension (ICE) were reviewed. The median age at diagnosis was 4 years. One patient had clear cell sarcoma (CCS); the remainder had favorable histologic findings (FH). The clinicopathologic stage was stage II in one patient, stage III in eight patients, and stage IV in six patients. ICE was detected before operation in six patients, during operation in five patients, and after operation in five patients. CPB was used in 10 patients. Eleven patients (73%) had operative complications, with major intraoperative hemorrhage occurring most often (six patients). Complications occurred less often when ICE was recognized before operation (three of six patients) than when it was not (eight of nine patients). Embolization occurred in only two patients. There were no operative deaths. The patient with CCS died. Eleven of 14 patients with FH survived, with an actuarial event-free, 2-year survival rate of 86%. There were no patients in the first NWTS. Of the six patients in the second NWTS (NWTS-2), four died (67%). All nine patients in the third NWTS (NWTS-3) survived, but follow-up was shorter (median 4 years 9 months vs. 2 years 7 months). No particular surgical procedure was associated with an increased death rate. This review suggests Wilms' tumor with ICE presents a formidable surgical undertaking but has a relatively good prognosis. Embolization is an uncommon event in ICE (two patients, 13.3%), allowing a planned operative approach. Echocardiography and ultrasonography provide accurate preoperative diagnosis. And ICE should be suspected in patients with extensive vena cava thrombosis or who have hypotension or heart failure during examination or surgery.

Primary malignant lymphoma of urinary bladder

A case of primary malignant lymphoma of the urinary bladder is described. The classic presentation of gross hematuria and dysuria with a benign clinical course is illustrated. From a review of the literature and our experience, we conclude that localized primary lymphoma of the bladder, especially those with favorable histologic findings, often does not require medical or surgical intervention. Persistent irritative bladder symptoms can be palliated adequately with external beam radiotherapy, while surgical intervention is rarely indicated.

Survival in Hodgkin Disease

A retrospective study of 250 patients with Hodgkin disease was done to compare 39 survivors of 10 years to 26 survivors of less than 3 years from time of diagnosis. Factors of significance between survivors of Hodgkin disease of less than three years and those of more than ten years are fever, weakness, cough, dyspnea, anorexia, extensive axillary or inguinal nodes, mediastinal involvement, performance status less than 90%, stage of disease at diagnosis (stage I or II), and favorable histologic findings (lymphocyte predominance or nodular sclerosing). Other factors are of less or little significance. The predominance of long-term survivors whose disease was diagnosed up to 1961 were in stage I or II by retrospective analysis. Long periods of remission between treatments correlated with long survival.