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Measurements of lung parenchyma, membranous bronchioles, and bronchial mucous gland hyperplasia were made on lungs from eight cases of pure centrilobular emphysema (CLE) and on five normal lungs. The lungs were fixed in formalin and inflated under partial vacuum at a standard transpulmonary pressure of +30 cm. HO. The results obtained from the upper halves and the lower halves of the lungs were compared. The circulatory effects of the disease were measured by weighing the heart ventricles, by studying the small pulmonary arteries in microscopical sections, and by post-mortem arteriography. Whereas the parenchymal and internal surface areas destroyed by the emphysematous spaces were relatively moderate and localized, right ventricular hypertrophy was noted in most of the cases. In these cases bronchiolar stenoses were found scattered throughout the whole lung and there was a reduction in the number of these bronchioles, mainly in the upper halves of the lungs. In CLE ventilatory disturbances were caused not only by the centriacinar dilated spaces delaying gas diffusion, but also by scattered bronchiolar stenoses situated at the termination of the conducting air passages. The stenoses seemed the more important cause. It was shown statistically that chronic arterial pulmonary hypertension and right ventricular hypertrophy were mainly the result of functional disturbances, especially hypoxia and abnormalities of VA/Q produced by the two structural changes situated at the end of the small airways. [ABSTRACT FROM PUBLISHER]

This study investigated the multidrug resistance, proliferation and apoptosis expression in renal cell carcinomas compared to adjacent normal kidney (ANK) tissues. Multidrug resistance (MDR1), multidrug resistance-associated protein (MRP), glutathione-S-transferase-pi (GST-pi), Topoisomerase-II alpha (TOPO-IIalpha), thymidylate synthase (TS), thymidine kinase (TK), Ki67, BAX and BCL-2 genes were analysed in a series of 30 renal cell carcinomas (RCC) and 16 biopsies from adjacent normal kidney (ANK) tissue using reverse-transcription-PCR (rt-PCR). The mean MDR1 expression was significantly lower in RCC than that of ANK (0.4 +/- 0.2 sd versus 0.75 +/- 0.19, p = 0.0008). The expression of MRP, GST-pi and TOPO-IIalpha was not significantly different in RCC as compared with ANK. The mean TK expression in RCC was significantly higher than in ANK (0.31 +/- 0.15 versus 0.09 +/- 0.08, p = 0.002). The TS and Ki67 expression in RCC was significantly higher than in ANK (87.5%, IC95% 71-100% versus 0%, p = 0.001; 56% IC95% 32-81% versus 0%, p = 0.004, respectively). BAX and BCL-2 expression in RCC was significantly higher than that of ANK (0.51 +/- 0.08 versus 0.18 +/- 0.12, p = 0.0001; 0.73 +/- 0.16 versus 0.5 +/- 0.22, p = 0.01, respectively). No significant correlation was found between MDR1, MRP, GST-pi, TOPO-IIalpha, TS, TK and BAX expression with the grade and the clinical stage in RCC.

To establish human renal cell carcinoma (RCC) xenografts for preclinical studies, 55 renal tumors (33 primary and 22 metastatic lesions) were transplanted subcutaneously into severe combined immunodeficient mice. Twenty of 49 evaluable tumors (40.8%) grew with a median latency period of 89 days (36 to 209 days) from the day of engraftment. Tumor growth was stabilized after the fifth passage with a median time between passages of 38 days (19 to 80 days). Tumorigenicity was correlated with the metastatic phenotype of the tumor (54% success rate, p = 0.007) and with reduced survival of patients. Despite a possible evolution of histological features and tumor grading, established RCC xenografts were comparable to parental tumors, as assessed by karyotype and DNA-ploidy analyses. Molecular cytogenetic analysis also revealed specific genetic alterations characterizing distinct RCC types that were constant in parental and corresponding xenografts. In addition, this xenograft model has permitted the selection of minor tumor subclones with a proliferative advantage and minimal overexpressed chromosomal regions. We conclude that severe combined immunodeficient mice are useful recipients for the establishment of long-term RCC xenografts that can be used as valuable tools to evaluate the activity of new therapeutic approaches and to study biological parameters determining in vivo aggressiveness of human RCC.

Two cases of papillary renal cell carcinoma (RCC) with a karyotype 46,X,t(X;1)(p11.2;q21) in two female patients aged 9 and 29 years are reported. These observations, and the review of the 17 reported cases with a translocation at band Xp11 confirm that this abnormality delineates a clinicopathological entity within the classical papillary RCC, characterized by the early age of occurrence and, probably, distinct histological features. Including these two new female cases, the sex ratio in cases with t(X;1) appears similar to that observed in the other papillary RCC.

Background/aims: Early liver transplantation is crucial in children with liver disease and pulmonary artery hypertension. Some severe pulmonary vascular anomalies associated with portal hypertension disappear after isolated liver transplantation. Evolution of pulmonary artery hypertension due to plexogenic arteriopathy is controversial, as this association is still considered a contraindication to isolated liver transplantation. Outcome of pulmonary hypertension after isolated liver transplantation is reported in three patients with portal hypertension., Methods: After echocardiographic diagnosis, the patients had a complete hemodynamic exploration, and two had a lung biopsy. After liver transplantation, the survivors had echocardiographic follow up and a second hemodynamic exploration., Results: In two children, pulmonary pressures and resistances returned to near-normal values 1 and 6 years after successful isolated liver transplantation. The third patient, with the most severe arteriopathy, had to wait 1 year for a donor, and the attempted transplantation was complicated by ventricular tachycardia; death occurred 2 days after surgery., Conclusions: Liver transplantation can reverse pulmonary artery hypertension due to high pulmonary resistances complicating liver disease with portal hypertension, provided it is carried out at an early stage. Early detection of pulmonary hypertension by systematic echocardiography may thus be crucial in these children with portal hypertension.

Objective: The prognostic significance of seminal vesicle invasion on the radical prostatectomy specimen was evaluated according to the proximal or distal site of this invasion., Materials and Methods: 52 consecutive patients undergoing radical prostatectomy for stage pT3b N0 M0 prostatic cancer were classified into two groups: group A (18 patients): patients with invasion limited to the proximal part of the seminal vesicles (stage T3b limited); group B (34 patients): patients with invasion extending to the free part of the seminal vesicles (stage T3b extensive). The PSA progression-free curves were compared between the two groups. A multivariable regression model was performed to determine independent prognostic factors., Results: Overall, the 5-year PSA progression free rate of the 52 patients was 14.4%. The 5-year PSA progression-free rate of the patients in group A was 45.4 vs. 4.2% at 4 years in group B (p = 0.0004). The stage of seminal vesicle invasion and the Gleason score were the only independent predictive factors of PSA progression (p = 0.02 and p = 0.04, respectively)., Conclusions: The prognostic significance of seminal vesicle invasion is not constant and depends on the site of invasion. Preoperative seminal vesicles biopsies can select patients with invasion extending to the free part of seminal vesicles and who have a poor prognosis in terms of PSA progression after radical prostatectomy.

Background: Renal oncocytoma has several features that overlap with other renal neoplasms, including the eosinophilic subtype of chromophobe cell carcinoma. In fact, strict criteria for renal oncocytoma have not been well defined and remain a matter of controversy. Ultrastructural studies or sophisticated methods such as flow cytometry and cytogenetic techniques can be of great use in distinguishing the two tumors, but are difficult to propose as routine methods because of their limited availability., Objective: To further characterize the histologic criteria of these tumors, we undertook a retrospective study to define the utility of routinely available histochemical and immunohistochemical techniques., Design and Setting: Twenty-one cases of chromophobe cell carcinoma, eosinophilic subtype, and 103 cases of oncocytoma were tested with histochemical (Perls, periodic acid-Schiff, and Hale's colloidal iron) and immunohistochemical (peanut agglutinin antigen and UEA-1 for lectins; cytokeratin KL1, epithelial membrane antigen, vimentin, S100 protein, and lysozyme) staining., Results: The antibodies tested and the histochemical staining using Hale's colloidal iron allowed eosinophilic chromophobe cell carcinoma to be distinguished by its characteristic reaction pattern. Seventy-six percent of the chromophobe cell carcinomas showed a microvacuolated pattern, and 89% of the renal oncocytomas showed an apical positivity with Hale's colloidal iron staining (P < .01). Peripheral cell accentuation reactivity for cytokeratin KL1 was observed in 66% of the chromophobe cell carcinoma cases, and apical cytoplasmic positivity was observed in 37% of the renal oncocytoma cases (P = .01). Significant patterns were observed with anti-epithelial membrane antigen and anti-peanut agglutinin antigen antibodies (P = .05 and P = .01, respectively). Positive reactions for vimentin, S100 protein, lysozyme, and UEA-1 were not significant characteristics., Conclusion: Our study demonstrated that a precise morphologic description associated with simple histochemical and immunohistochemical techniques provides sufficient criteria for a high level of discrimination between the eosinophilic subtype of chromophobe cell carcinoma and renal oncocytoma.

Tumor-infiltrating lymphocytes (TIL) were grown from 23 urothelial carcinomas. Phenotyping analysis showed that the TIL cultures were mainly CD3+. Although CD4+ and CD8+ T-cell sub-sets were grown in culture, CD4+ T-cell sub-sets predominated over CD8+ T cells. Immunohistochemical studies performed on 5 tumor specimens confirmed this observation, and indicated that CD4+ T cells surrounded the tumor islets, whereas CD8+ T lymphocytes were localized among the tumor cells. Five short-term carcinoma cell lines established from these urothelial tumors were used as target cells in cytolysis assays in order to investigate the functional anti-tumor activity of autologous TIL. TIL from 4/5 tumors were lytic and 3 TIL lines displayed MHC-class-I-dependent cytotoxicity directed against autologous tumor cells. CD4+ T-cell-depletion experiments performed on TIL line 07 confirmed that CD8+ MHC-class-I-dependent CTL were the predominant effectors. Finally, experiments performed on 6 allogeneic urothelial-cancer cell lines matched for HLA-class-I molecules showed that TIL07 exhibited selective lytic activity toward tumor 07. These data indicate that CD8+ MHC-class-I-dependent CTL present in urothelial carcinomas are functional and may participate in the anti-tumor immune response.

Objective: To identify patients at high risk of extraprostatic seminal vesicle infiltration, in whom preoperative seminal vesicle biopsies should be performed., Materials and Methods: We studied the relationship between extraprostatic seminal vesicle infiltration and the available preoperative data [age, clinical stage, prostate-specific antigen (PSA) level, number and site of positive prostatic sextant biopsies, Gleason score] in a total of 75 patients suffering from clinically localized prostatic adenocarcinoma who were candidates for radical prostatectomy., Results: The chi 2 test showed that the preoperative data most significantly correlated with extraprostatic seminal vesicle infiltration were the presence of positive basal biopsies (p < 0.001). The PSA level did not have any predictive value. The most discriminant preoperative parameter of the state of the seminal vesicles (analysis of variance on a univariate model) was the state of the basal prostatic biopsies. The importance of this parameter was confirmed by cluster analysis. Overall, the risk of extraprostatic seminal vesicle invasion was 0 (0/21 patients) when the 2 basal prostatic biopsies were negative, 10.25% (4/39 patients) when 1 of the 2 basal prostatic biopsies was positive and 73.33% (11/15 patients) when both basal prostatic biopsies were positive., Conclusions: In a patient with clinically localized prostatic adenocarcinoma who is a candidate for radical prostatectomy, seminal vesicle biopsies are useless when basal prostatic biopsies are negative, regardless of the state of other preoperative parameters. When 1 or 2 basal prostatic biopsies are positive, seminal vesicle biopsies can improve the pretreatment pathological staging.

Purpose: To identify prognostic factors of improved survival after resection of isolated pulmonary metastases (PM) from colorectal cancer., Patients and Methods: A retrospective analysis of the records of all patients with PM from colorectal cancer who underwent thoracic surgery with curative intent before December 1992 at a single surgical center was performed. Univariate (log-rank) and multivariate (Cox's model) analyses of survival were used to identify significant prognostic factors., Results: Eighty-six patients with PM from colon (n = 49) or rectal (n = 37) cancer underwent 102 thoracic operations, which included 21 bilateral and 10 incomplete resections. The 5- and 10-year probabilities of survival (Kaplan-Meier) after the first thoracic operation were 24% (95% confidence interval [CI], 15% to 35%) and 20% (95% CI, 13% to 31%), respectively. Sex, age, site of the primary tumor (colon or rectum), disease-free interval (DFI), and previous resection of hepatic metastases were found not to be statistically significant prognostic factors. Complete resection, a limited number ( < two) of PM, and a normal prethoracotomy serum carcinoembryonic antigen (CEA) level were predictors of a longer survival duration by univariate analysis, but only complete resection (P = .024) and preoperative CEA level (P = .001) were identified as independent prognostic factors by multivariate analysis. The estimated 5-year survival rate of patients with a normal prethoracotomy CEA level was 60%, as compared with 4% in cases with elevated ( > 5 ng/mL) CEA level., Conclusion: Besides resectability, the prethoracotomy serum CEA level appears the most reliable predictor of survival in patients with isolated PM from colorectal cancer.

Human chorionic gonadotropin (hCG) and its beta sub-unit (hCG beta) are secreted by trophoblast cells during pregnancy, and by tumoral cells of trophoblastic and non-trophoblastic origin. In contrast to hCG, the free hCG beta sub-unit is consistently undetectable in healthy non-pregnant subjects. With this in mind, we sought to determine whether an immune response to hCG beta can be detected in patients with bladder or germ-cell testis cancers. Peripheral-blood mononuclear cells (PBMC) from 31% of patients with hCG beta-productive bladder cancers and 33% of testis-tumor-bearing patients displayed an hCG beta-specific proliferative response, whereas no patients with non-hCG beta-productive cancers had a proliferative response. PBMC from pregnant women and healthy controls did not elicit significant reactivity. By the use of overlapping synthetic peptides, the immunogenic regions of hCG beta were delineated within the central 20-65 portion. Moreover, in 2 bladder-cancer patients with the HLA DR7, DQ2 haplotype, the T-cell response to hCG beta was focused on the hCG beta (20-47) peptide. Taken together, these results indicate that hCG beta is a tumor-associated antigen capable of inducing a cell-mediated immune response in patients with productive tumors.

A total of 71 patients with clinically localized prostatic cancer underwent preoperative biopsy of each seminal vesicle. Group 1 (67 patients) underwent 2 seminal vesicle biopsies before lymph node dissection and vesiculo-prostatectomy, while group 2 (4 patients) underwent seminal vesicle biopsy and lymph node dissection before radiation therapy. In group 1 there were 11 positive biopsies (16.5%) with a median prostate specific antigen (PSA) level of 24 ng./ml. (range 11 to 45). Of the biopsies 56 were normal, with a median PSA level of 11.8 (range 3.5 to 88, p < 0.008). Histological examination of the seminal vesicles on the prostatectomy specimen revealed 18 cases of seminal vesicle invasion (sensitivity 61%, specificity 100%, positive predictive value 100% and negative predictive value 87.5%). A positive biopsy was correlated with the mean tumor volume (10.3 cc with positive biopsies versus 4.9 cc with negative biopsies) and local invasion (positive margins in 36% versus 9%, respectively, and capsular perforation in 81% versus 25%, respectively). In group 2 the 4 seminal vesicle biopsies and lymph node dissections were positive. Overall (groups 1 and 2), positive seminal vesicle biopsies were predictive of lymph node involvement in 47% of the cases versus 7% when biopsies were negative (p > 0.001). The postoperative course was significantly different (local recurrence and metastases in 45% versus 9%, respectively, and median interval 8.8 months versus 18.3 months, respectively, p < 0.001). Seminal vesicle biopsy appears to have a satisfactory yield only in cases with a PSA level of greater than 10 ng./ml. A positive seminal vesicle biopsy confirms the presence of extraprostatic invasion of clinically localized cancer in a given patient. Seminal vesicle biopsy allows for better staging of prostatic cancer.

Objective: Special emphasis has been placed on pathologic features, survival after surgical treatment, and prognostic factors., Summary Background Data: Incidence is much lower in Western countries than in Japan. All degrees of tumor differentiation met in invasive cancer may be found. Prognosis is remarkably good, compared with advanced gastric cancer., Methods: After reexamination of the pathologic specimens of 115 patients, 101 patients were included in this study; 58 were male. Mean age was 60.7 years. Preoperative biopsies were positive in 88%. The lesion was located in the antrum in 78 patients. Subtotal gastrectomy was performed in 85 patients and total gastrectomy in 13 patients with a RI lymph node resection., Results: Cancer was extended to submucosa in 68.3%, poorly differentiated in 48.5%, and multifocal in 12.9% of patients. Lymph node involvement was present in 18.8%. Secondary deaths (n = 25) were in relation with the cancer in 6 patients only. The 5-, 10-, 15-, and 20-year actuarial crude survival rates were 88, 65, 58, and 51%, respectively. The survival rate was significantly higher for mucosal lesions than for submucosal lesions (p < 0.01). Survival showed no significant correlation with lymph node involvement, tumor size, and differentiation., Conclusions: Subtotal gastrectomy is recommended, except for proximal lesions, with survey of the gastric stump. Prognosis is significantly better for cancers limited to mucosa. Early gastric cancer is not a specific entity. Transitions between early and advanced carcinomas, especially observed in the poorly differentiated carcinomas with signet ring cells, suggest that this type of cancer should be a precursor of the invasive gastric carcinomas.

A system generating focused elastic ultrashort waves has been developed with the aim to destroy tumors by an extracorporeal way. Experimental studies on different targets (plastic phantoms, organ samples and normal live tissues in pigs) have been done showing the good focusing of the device and the possibility of getting a focal tissular coagulative necrosis. Studies on cultured tumor cells and implanted tumors in rats have shown a local effect on cells or tumor growth with the absence of metastatic risks. First human trials are summarized. This technique we call focused extracorporeal pyrotherapy could be useful for the treatment of cancers.

An enlargement of the thymus suggesting a tumor was discovered in a 28-year-old man who had early-stage acquired immune deficiency syndrome. A biopsy was performed. The adipose involuted thymus, with persistence of many Hassall's corpuscles, was judged to be a large lymphoid follicular hyperplasia. This follicular hyperplasia was similar to that previously described for lymph nodes, spleen, and other lymphoid tissues at earlier stages of human immunodeficiency virus infection, before the development of acquired immune deficiency syndrome. Human immunodeficiency virus RNA and p24 human immunodeficiency virus protein were detected in the hyperplastic germinal centers (lymphocytes and follicular dendritic infected cells), and also in many cells that may have been either lymphocytes and/or epithelial cells in the interfollicular areas. The tissue was negative for Epstein-Barr virus DNA sequences, as determined by the polymerase chain reaction. These observations identify the first state of infection of the thymus in a human immune deficiency virus-infected adult, preceding the severe involution with lymphoid depletion observed in all fatal cases of acquired immunodeficiency syndrome in which the thymus has been analyzed.

A new device made of piezoelectric ceramic placed in a semispherical dish and focussed at 320 mm was developed in order to generate heat and cavitation responsible for coagulative necrosis of deep tissues. The target to be treated is located with a central ultrasound probe of 3.5 MHz. In vitro studies with polyurethane phantoms showed that the ultrasound melted a surface of 2 x 12 mm within 1 s. The temperature recorded at the focus was 270 degrees C. In tissue samples (prostate cancer and benign prostate hyperplasia), the temperature rose to 85 degrees C in vitro and a hyperechoic zone appeared at the focus during shots. In vivo 8-mm plastic spheres, introduced surgically into the bladder of pigs, were melted by repeat shots without burning of crossed tissues. These studies were performed in the kidney and the liver. Autopsy performed on day 0 showed congestion, autopsy performed between day 6 and day 11 showed necrosis, whereas at 3 months the focussed area was fibrosed. This technique, which we called 'focussed extracorporeal pyrotherapy', combines phenomena of cavitation and high heat at the focus. Prostate tumors, bladder tumors, kidney tumors and liver metastases are potential indications for pyrotherapy.

Twenty-five patients with localized prostate cancer underwent seminal vesicle biopsies before radical prostatectomy. A transrectal probe of 7 MHz, a 18-gauge needle and a biopsy gun were used. The preoperative biopsy established the absence of seminal vesicle invasion in 89% of cases. When the seminal vesicles are positive at biopsy, capsular penetration is observed in 100% of the cases and lymph node positivity in 50%. When seminal vesicles are negative at biopsy and the prostate-specific antigen level is less than 20 ng/ml (n less than 2.5), capsular penetration of greater than 1 cm is absent in 100% of cases and lymph nodes are positive in only 7% of cases. Biopsy of the seminal vesicle, as an outpatient procedure, improves the preoperative staging of prostate cancer before radical prostatectomy: negative biopsies are good predictors of the absence of lymph node invasion.