Manuel Sánchez-Chapado

Renal Echinococcosis: Clinical Study of 34 Cases

PURPOSE Hydatid disease, a cyclo-zoonotic parasitic infestation caused by the larval stage of the cestode Echinococcus granulosus, is prevalent worldwide. We reviewed the clinical findings of a large series of renal hydatidosis treated in an endemic area with special emphasis on diagnostic pitfalls. MATERIALS AND METHODS A retrospective 15-year review in a rural area of central Spain (600,000 population), with a global incidence of hydatidosis of 10 new cases per 100,000 population per year, revealed 34 with renal echinococcosis treated surgically (3 to 4% of officially confirmed cases of hydatidosis). Clinical, radiological and laboratory data were analyzed. RESULTS Renal hydatid disease mimicked other diseases. The combination of clinical history, imaging studies, and serological and urine investigation yielded a reliable pretreatment diagnosis in only 50% of cases and a presumptive diagnosis in 71%. Among imaging studies computerized tomography was the most valuable diagnostic examination. Moderate eosinophilia was found in half of the cases, while a third had scoleces in the urine. A diagnostic and therapeutic algorithm is presented. CONCLUSIONS Preoperative diagnosis of renal hydatid disease is difficult even in an endemic zone. Imaging studies are suggestive but usually inconclusive, and the differential diagnosis with a renal tumor or complicated cyst may not be made without surgery. Renal sparing surgery is possible in a significant proportion of cases, particularly when preoperative diagnosis has been considered. Significant surgical morbidity can be expected, and the risk of anaphylaxis and hydatid seeding, although low, should not be overlooked.

ISOLATED RETROVESICAL AND EXTRARENAL RETROPERITONEAL HYDATIDOSIS: CLINICAL STUDY OF 10 CASES AND LITERATURE REVIEW

PURPOSE Isolated extrarenal retroperitoneal echinococcal cyst is a rare manifestation of hydatid disease. We review the clinical findings of a series of isolated retrovesical and retroperitoneal hydatid cysts in an endemic area, with special emphasis on diagnostic pitfalls. MATERIALS AND METHODS A retrospective 15-year review in a rural area of central Spain (600,000 population), with a global incidence of hydatidosis of 10 new cases per 100,000 population per year, revealed 10 patients (0.1 cases per 100,000 per year) with surgically treated primary extrarenal retroperitoneal echinococcosis and absence of other hydatid cysts in any organ. Clinical, radiological and laboratory data are analyzed. The literature of the last 15 years on hydatid disease with a primary retroperitoneal and retrovesical location is reviewed. RESULTS A total of 42 cases of isolated retrovesical (25) and retroperitoneal (17) hydatidosis was compiled. Male predominance of 2.5:1 was noted and age ranged from 8 to 79 years (mean 42.2 +/- 5.4). The most frequent presentation was a palpable mass in 29% of the cases followed by flank pain in 24%, frequency in 17% and urinary retention in 14% of the cases. Hydatiduria of the urinary tract was present in 9.5% of the cases. Different serological investigations were performed in 45% of the cases with positive results in 68%. The lesion had been surgically removed in all cases. Therapy and followup of each patient were analyzed. CONCLUSIONS An isolated retrovesical, retroperitoneal or even retrocrural cyst can be the unique manifestation of hydatid disease. Although difficult, preoperative diagnosis is desirable for the selection of a surgical approach and prevention of allergic reactions and operative spillage. A diagnostic algorithm and several therapeutic guidelines are proposed.

Transforming Growth Factor β and its Receptor Types I and II. Comparison in Human Normal Prostate, Benign Prostatic Hyperplasia, and Prostatic Carcinoma

An immunohistochemical and semiquantitative comparative study of transforming growth factor beta 1 (TGF-beta 1) and its receptor types I (TGF-beta RI) and II (TGF-beta RII) was carried out in normal prostates and in the prostates from men with benign prostatic hyperplasia (BPH), and men with prostatic adenocarcinoma. Immunoreaction to TGF-beta 1 was limited to the basal epithelial cells in the normal prostates. Some cells in the connective tissue stroma were also stained. In BPH immunolabelling was also observed in columnar (secretory) cells of the epithelium. In prostatic adenocarcinoma, all epithelial cell types were intensely immunostained. Some stromal cells were also stained. Immunostaining to TGF-beta RI was only present in the basal cells in normal prostates. In BPH, this immunoreaction was found in the whole epithelium and in some stromal cells. In prostatic cancer, the immunostaining pattern for this receptor was similar to that of BPH but more intense in the epithelial cells. Immunoreactivity to TGF-beta RII appeared in some basal cells and some scattered columnar cells of the normal prostate epithelium. In the BPH sections, this pattern was maintained, and a weak immunolabelling was also observed in the stroma. In prostate cancer, all epithelial cells appeared intensely labelled. In the stroma, immunolabelling was similar to that of the BPH specimens. The results of the present study suggest that, in normal prostates, only the basal cells of the epithelium possess both receptor types, and hence can transduce TGF-beta 1 signal intracellularly. The basal cells can also secrete this growth factor which would act as an autocrine inhibitory growth factor for them. In addition, TGF-beta 1 is secreted in some zones by stromal cells, acting then as a paracrine growth factor for basal cells in those areas. In BPH, in addition to the basal cells, some secretory columnar cells also secrete TGF-beta 1 and possess both types of TGF-beta 1 receptors, and thus, both epithelial cell types are susceptible to TGF-beta 1 action. Since both receptor types are also present in some stromal cells, these cells also perform an autocrine secretion, in addition to their paracrine secretion to the epithelial cells. TGF-beta RIIs seem to be more numerous than TGF-beta RIs and this lead us to hypothesize that these incomplete receptors might be a protection against the inhibition caused by TGF-beta 1 action. In prostatic carcinoma all cell types display the same characteristics as in BPH, although both receptor types are found in similar numbers, and thus, the above mentioned protection would not occur.

A lectin histochemistry comparative study in human normal prostate, benign prostatic hyperplasia, and prostatic carcinoma.

The partial oligosaccharide sequences of glycoconjugates and the nature of their glycosidic linkages were investigated in normal human prostate, benign prostatic hyperplasia (BPH) and prostatic carcinoma by means of lectin histochemistry, using light microscopy and Western blot analysis. The labeling pattern of BPH differed from that of normal prostate in having more intense staining with DSA, HPA, UEA-I and AAA, and in showing lesser staining with WGA and SBA. Prostatic carcinoma differed from normal prostates in displaying the more intense labeling with PNA, DSA, SBA, DBA, UEA-I and AAA, and in having lesser labeling with WGA. The main differences in labeling pattern between prostatic carcinoma and BPH were that the latter specimens showed more marked staining with PNA, DSA, DBA, SBA, UEA-I and AAA, and lesser staining with WGA and HPA. The staining patterns of SNA, MAA, ConA, LCA and GNA were similar in all three groups of specimens. For most of the lectins studied, including those showing a similar immunohistochemical staining in the three groups of specimens studied, the Western blot analysis showed differences in the banding pattern among normal, hyperplastic, and carcinomatous prostates. Present results suggest that the glycosylation of proteins was modified in both BPH and prostatic carcinoma. In BPH a strong expression of N-acetylgalactosamine residues occurred, while in prostatic carcinoma an increase of sialic aci, galactose and fucose residues was observed. No changes in mannose residues were detected.

Primary Cisplatin, Methotrexate and Vinblastine Aiming at Bladder Preservation in Invasive Bladder Cancer: Multivariate Analysis on Prognostic Factors

PURPOSE Although radical cystectomy is the standard therapy for invasive bladder cancer, cisplatin based multi-drug chemotherapy has proved to be effective for advanced transitional cell urothelial carcinoma. The potential for bladder preservation with neoadjuvant chemotherapy is currently under investigation. MATERIALS AND METHODS A phase 2 protocol is presented for conservative treatment of muscle invasive transitional cell carcinoma of the bladder consisting of primary cisplatin, methotrexate and vinblastine chemotherapy followed by reevaluation for bladder sparing surgery and surveillance. A total of 61 patients completed the protocol with a mean followup of 41.4 months. RESULTS Initial complete response to chemotherapy associated with tumor stage, size and configuration was noted in 20 patients (33%). Bladder preservation, intended only for the complete response group, was achieved in 16 patients (26%) but only 11 (18%) were alive with the bladder intact at study closure. Disease-free 5-year survival rate was 47% (95% confidence interval 65 to 26%). Tumor stage (p = 0.0007), size (p = 0.0003), response to chemotherapy (p = 0.002), patient age (p = 0.039) and tumor grade (p = 0.048) influenced survival. Multivariate analysis revealed response to chemotherapy (beta = 0.988, p = 0.034) and tumor size (beta = 0.978, p = 0.042) to be the only independent predictors. CONCLUSIONS Induction of cisplatin, methotrexate and vinblastine chemotherapy is helpful in identifying patients with a greater chance for survival among those with locally advanced bladder cancer. However, a bladder preservation strategy based on this therapy is only of limited success.

One-incision nephroureterectomy endoscopically assisted by transurethral ureteral stripping

OBJECTIVES Ureteral endoscopic surgery has been proposed as the first step of nephroureterectomy, either open or laparoscopic, to obviate the low abdominal incision. We present our experience with a technique of one-incision nephroureterectomy endoscopically assisted by transurethral ureteral stripping. METHODS Standard nephrectomy is performed after placement of a Chevassu ureteral catheter. The lumbar ureter is sectioned and the catheter tip tied to the top of the distal portion of the ureter, which is later intussuscepted when the catheter is pulled out. Transurethral resection through the muscular wall and into the perivesical fat is performed around the everted ureteral orifice, and the bladder spontaneously closes with an indwelling Foley catheter. Since 1989, we have used this technique in 21 patients with urothelial malignancies of the renal pelvis or calyces (15 patients), renal cell carcinoma (2 patients), renal cholesteatoma (1 patient), or reflux nephropathy (3 patients). RESULTS Two patients required a low abdominal incision for removal of retained ureter after unsuccessful stripping. The rest underwent this procedure without complications or adverse effects. Mean follow-up was 44.6 +/- 11.4 months (range 4 to 76). Three patients presented with bladder tumor but no recurrences were detected in the resected area of the bladder or the retroperitoneum. CONCLUSIONS Endoscopically assisted nephroureterectomy allows removal of an adequate cuff of bladder with the distal ureter and generally obviates extending the incision or performing a second one. It can be an attractive option in selected cases, without apparent risk of neoplastic urine contamination in the retroperitoneum.

Successful Conservative Management of Emphysematous Pyelonephritis, Bilateral or in a Solitary Kidney

Emphysematous pyelonephritis, bilateral or in a solitary kidney, is a life-threatening condition that requires prompt diagnosis and early intervention. Reported mortality is high, despite desperate surgical measures often ending in loss of renal unit, but medical management, possibly combined with percutaneous drainage, is sometimes successful. We report two cases of emphysematous pyelonephritis, one bilateral and one in a solitary kidney, with successful conservative management. Predisposing factors were insulin-dependent diabetes mellitus and micronodular cirrhosis secondary to chronic alcoholism. Prompt sonographic diagnosis determined the success of conservative management. Escherichia coli was identified as causal factor. In the bilateral case the clinical picture improved within 48 h after control of diabetes and broad-spectrum antibiotic treatment. For the affected solitary kidney, percutaneous drainage and ureteric catheterization were required.

A DNA hypermethylation profile reveals new potential biomarkers for prostate cancer diagnosis and prognosis.

DNA hypermethylation has emerged as a novel molecular biomarker for the evaluation of prostate cancer diagnosis and prognosis. Defining the specific gene hypermethylation profile for prostate cancer could involve groups of genes that specifically discriminate patients with indolent and aggressive tumors.

Clinical significance of both tumor and stromal expression of components of the IL-1 and TNF-α signaling pathways in prostate cancer

IL-1 and TNF-α, the two major proinflammatory cytokines, have been involved in initiation and progression of several malignancies. They could influence the biological behavior of prostatic tumors and patient outcome, and could be useful as prognostic factors. This study evaluated the prognostic capability for biochemical progression after radical prostatectomy of expression of IL-1, TNF-α and related signaling components, in the tumor and surrounding stroma, as well as its correlation with other clinicopathological features. Expression of IL-1α, IL-1β, IL-1Ra, IL-1RI, IL-1RII, IRAK-1, TRAF6, TNF-α, TNFRI and TRAF2 was analyzed by immunohistochemistry in radical prostatectomy samples from 93 prostate cancer patients. Spearmans test, Kaplan-Meier curves, and univariate and multivariate Cox proportional hazard regression analyses were performed. Expression of TNF-α, TNFRI, TRAF2, ILRI, IRAK-1 and TRAF6 correlated with at least one clinicopathological feature (clinical T stage, pathological T stage, preoperative serum PSA or Gleason score). Increased tumor expression of TNF-α, TNFRI and IL-1RI, and reduced tumor expression of IRAK-1 were significantly correlated with a poor prognosis in univariate analysis. Reduced stromal expression of IL-1β and IL-1RII, and increased stromal expression of IRAK-1 were also adverse prognostic factors in univariate analysis. Remarkably, tumor IL-1β and stromal IL-1RII and IRAK-1 remained as independent prognostic factors after adjustment for preoperative serum PSA, pathological T stage and Gleason score in multivariate Cox models. Our results suggest that prostatic expression of TNF-α, IL-1β and related signaling proteins (TNFRI, IL-1RI, IL-1RII and IRAK-1) predicts clinical outcome in prostate cancer, and support the involvement of TNF-α and IL-1β signaling in prostate cancer progression.

Vasoactive intestinal peptide (VIP) induces malignant transformation of the human prostate epithelial cell line RWPE-1.

The carcinogenic potential of vasoactive intestinal peptide (VIP) was analyzed in non-tumor human prostate epithelial cells (RWPE-1) and in vivo xenografts. VIP induced morphological changes and a migratory phenotype consistent with stimulation of expression/activity of metalloproteinases MMP-2 and MMP-9, decreased E-cadherin-mediated cell-cell adhesion, and increased cell motility. VIP increased cyclin D1 expression and cell proliferation that was blocked after VPAC(1)-receptor siRNA transfection. Similar effects were seen in RWPE-1 tumors developed by subcutaneous injection of VIP-treated cells in athymic nude mice. VIP acts as a cytokine in RWPE-1 cell transformation conceivably through epithelial-mesenchymal transition (EMT), reinforcing VIP role in prostate tumorigenesis.