Detubularized folded O-shaped ileal bladder

Using a submucosal needle tunneling technique for ureteral implantation, detubularized folded O-shaped ileal bladders were created for seven patients in need of bladder replacement. A segment of ileum of only 300 to 400 mm in length was required. Anastomosis of the reservoir to the urethra was simply performed by tailoring the ileum to reduce tension at the anastomosis site. Follow-up periods ranged from 24 to 46 months. Excellent upper tract function and good evacuation function with minimal residual urine were demonstrated. Urodynamic studies revealed a mean bladder capacity of 367 mL, with low intra-ileobladder pressure. All patients are continent during the day. Mild enuresis was noted in three patients. No reflux was noted on follow-up voiding cystourethrography. This type of ileal bladder is simple to create and provides reliable results. The presence of a short mesentery is not a serious limiting factor.     

IL-4- and IL-5-secreting lymphocyte populations are preferentially stimulated by parasite-derived antigens in human tissue invasive nematode infections

Helminth infections in humans and animals are associated with strong T helper 2 (Th2) responses. To determine whether parasite-derived Ag preferentially expand a Th2-like cell population, a filter immunoplaque assay was used to enumerate the frequencies (F0) of PBMC and CD4(+)-enriched PBMC from individuals with helminth infections secreting selected cytokines in response to parasite-derived (PAg) and nonparasite antigens (NPAg). In 20 individuals with lymphatic filariasis, frequency analysis of PBMC secreting IL-4 and IFN-gamma indicated that the F0 of PAg-specific IL-4-secreting cells (geometric mean F0 (GM): 1/12,100) was 57-fold higher than the corresponding F0 of NPAg-reactive cells (GM: 1/692,000; p < 0.02). In marked contrast, the F0 of IFN-gamma-secreting cells responding to PAg (GM: 1/2,700) did not differ from those of cells specific for NAPg (GM: 1/3,400; p = 0.83). In another group of helminth-infected individuals, the F0 of highly enriched CD4+ cells secreting IL-4 and IL-5 in response to PAg (GMs: 1/2,600 and 1/5,600 CD4+ cells, respectively) were also found to be significantly higher than those specific for NPAg (GMs: 1/291,000 and 1/303,000 CD4+; p < 0.05 and p < 0.01, respectively), whereas the corresponding F0 of IFN-gamma- and granulocyte-macrophage-CSF-secreting cells were equivalent for PAg and NPag. Furthermore, the proportion of PAg-specific IL-4- and IL-5-secreting CD4+ cells relative to all cells secreting the given cytokine were approximately 29-fold higher than the proportion of NPAg-specific cells secreting these cytokines. Again, the corresponding proportions of Ag-specific IFN-gamma-and GM-CSF-secreting CD4+ cells were equivalent for PAg and NPAg. Thus, in this ex vivo system, a circulating population of IL-4- and IL-5-secreting (Th2-like) cells has been shown to exist in humans; PAg appears to expand these cells preferentially.     

The histological response to chemotherapy as a predictor of the oncological outcome of operative treatment of Ewing sarcoma

Seventy-four patients who had a Ewing sarcoma of bone were managed with preoperative and postoperative chemotherapy and operative resection, with or without postoperative irradiation. The primary objectives of the study were to determine the histological response to preoperative chemotherapy in terms of the percentage of tumor necrosis and to assess the relationship between the histological response and the oncological outcome. The minimum duration of follow-up of the surviving patients who were continuously free of disease was five years. Sections of each operative specimen were examined, and the histological response to chemotherapy was graded semiquantitatively. Grade I indicated necrosis of 50 per cent of the tumor or less; grade II, necrosis of more than 50 per cent but less than 90 per cent; grade III, necrosis of 90 to 99 per cent; and grade IV, necrosis of 100 per cent of the tumor. Of the seventy-four tumors, forty-four (59 per cent) were exquisitely sensitive to chemotherapy and had complete (grade-IV) or nearly complete (grade-III) necrosis. In contrast, fourteen tumors (19 per cent) had little or no response to chemotherapy (grade I) and sixteen (22 per cent) had a moderate degree of necrosis (grade II). The histological response to preoperative chemotherapy (p = 0.0001), followed by the size of the tumor (p = 0.001), were the most important predictors of event-free survival. At five years, the rate of event-free survival was zero of fourteen patients who had had a grade-I response, six of sixteen who had had a grade-II response, and thirty-seven (84 per cent) of forty-four who had had a grade-III or IV response. The risk of local recurrence was most strongly associated with the operative margins; there were only four local recurrences (6 per cent) after sixty-seven resections with negative margins. Local recurrence may also have been influenced by the histological response and the use of local radiation. There were no local recurrences after operative treatment of six tumors that had been associated with pathological fracture. The histological response to preoperative chemotherapy and the size of the primary tumor are the most important clinical predictors of the outcome of operative treatment of non-metastatic Ewing sarcoma. These indicators should be used to identify patients who are at high risk for metastasis as such patients may be candidates for more intensive or novel therapies.