Electric fusion of unfertilized starfish oocytes

BACKGROUND: Local failure rates are high for locally irresectable primary or recurrent colorectal cancer, even when chemoradiation therapy is employed. AIM: This review evaluates evidence supporting aggressive preoperative chemoradiation followed by maximal surgical resection and intraoperative radiation therapy to achieve disease control and cure for patients with locally advanced irresectable primary or recurrent rectal cancer. RESULTS: A 5-year survival rate of 42 per cent with a central failure rate of 2 per cent may be achieved in patients with locally irresectable primary rectal cancer. In patients with locally recurrent disease, these values at 5 years are 18 and 28 per cent respectively. The 5-year incidence of distant metastasis remains high, affecting 64 per cent of patients with primary cancer and 75 per cent of those with recurrent cancer. CONCLUSION: A disease-free surgical resection margin remains paramount to achieve cure. Encouraging trends exist, however, for further evaluation of multimodality therapy as a means of reducing local recurrence of disease.     

Adjuvant radiation therapy in resectable rectal cancer: should local recurrence rates affect the decision?

Adjuvant external beam pelvic radiotherapy (XRT) for resectable rectal cancer has been mandated by the National Cancer Institute because of reported 20 to 50 per cent reductions in local recurrence rates. However, these series' reported local recurrence rates are 18 to 39 per cent in the nonradiated patients, which seems extraordinarily high compared to the 3 to 5 per cent rates reported by surgeons advocating proctectomy with complete mesorectal excision. This fact, coupled with the high cost of XRT ($11,000-$14,000), the risk of radiation injury to small bowel and the neo-rectum, and the failure of XRT to provide any survival advantage, raises questions as to the precise role of XRT for rectal cancer. The purpose of this study was to perform a review of 212 consecutive patients undergoing curative resection via low anterior resection (LAR) or abdominoperineal resection (APR) for rectal cancer between 1989 and 1993, focusing on local and distant recurrence rates and survival. The choice of surgery alone (SUR), preoperative radiation (PRE) (45 Gy), or postoperative radiation (POST) (45-50 Gy) was at the surgeon's discretion. There were no significant differences in male:female ratio (SUR, 83:60; PRE, 14:8; POST, 34:13) or type of procedure (SUR-LAR, 112:APR, 31; PRE-LAR, 5:APR, 17; POST-LAR, 30:APR, 17) between the groups. There were no significant differences in age between the preoperative and postoperative radiation groups (PRE, 64.0 +/- 2.4; POST, 59.2 +/- 1.7); however, age was significantly different (P < 0.05) between the surgery-alone and the postoperative radiation groups (SUR, 68.5 +/- 0.8; POST, 59.2 +/- 1.7). With a median follow-up of 49 months, there were no significant differences in local recurrence (SUR, 4.2%; PRE, 4.5%; POST, 2.1%); however, there was a significantly longer survival for the SUR group compared to the other groups (SUR, 45.9 months; PRE, 36.4 months; POST, 39.3 months; P < 0.05 least significant difference). The PRE group also had shorter survival compared to the other groups when only Stage II and III lesions were studied (S, 40.0 months; PRE, 28.3 months; POST, 39.3 months). Local recurrences based on TNM stage were: T1N0 (S, 0 of 27; PRE, 0 of 3); T2N0 (S, 4 of 4S; PRE, 0 of 7); T2N1 (S, 0 of 9; POST, 1 of 5); T3,4N0 (S, 2 of 37; PRE, 1 of 9; POST, 0 of 10); and T3,4N1,2 (S, 0 of 21; PRE, 0 of 3; POST, 0 of 30). The results of this series support the contention that proctectomy with complete mesorectal excision yields a 4.2 per cent local recurrence rate without the need for adjuvant XRT. In this series, if all the patients had received adjuvant radiation, an additional $2.2 million would have been added to the costs of medical care. Therefore, the potential risks, costs, and benefits of adjuvant pelvic XRT for rectal cancer must be weighed against optimal benchmarks for local recurrence rate for surgery alone.     

A reproducible method for automated extraction of brain volumes from 3D human head MR images

PURPOSE: To assess the frequency and prognosis of skin recurrences after breast-conserving therapy (BCT) compared with other breast recurrences. MATERIALS AND METHODS: From 1968 to 1986, 1,624 patients with unilateral stage I or II breast cancer treated with BCT at the Joint Center for Radiation Therapy (Boston, MA) underwent gross tumor excision and received a dose of > or = 60 Gy to the tumor bed. Skin recurrences (SR) were defined as breast recurrences without associated parenchymal disease. An invasive breast recurrence with any parenchymal disease noted clinically or radiographically was scored as an other breast recurrence (OBR). Median follow-up for survivors was 137 months. RESULTS: SR represented 8% (18 of 229) of all breast recurrences and occurred in 1.1% of all patients. The outcome after local recurrence was different for patients with SR and invasive OBR. Patients with SR more frequently had uncontrolled local failure (50%; 9 of 18) than did patients with OBR (14%; 26 of 188) (P = .0007). Forty-four percent (8 of 18) of patients with SR had distant metastasis simultaneously or within 2 months of the recurrence compared with 5% (9 of 188) of invasive OBR patients (P < .0001). For patients without distant metastasis at the time of recurrence, the 5-year actuarial rate of development of distant metastasis was 60% for SR patients compared with 39% for invasive OBR patients (P = .07), and the corresponding 5-year actuarial survival rates beyond the time of local failure were 51% and 79%, respectively (P = .06). CONCLUSION: In contrast to other types of invasive breast recurrence after breast-conserving therapy, skin recurrences are rare and are associated with a significantly higher rate of distant metastasis and uncontrolled local disease as well as a lower rate of survival.     

In vivo tendon forces correlate with activity level and remain bounded: evidence in a rabbit flexor tendon model

The purpose of this study is to assess the feasibility, clinical tolerance, local control, and survival rates using a combined-modality treatment program of intraoperative radiation, chemotherapy, and external beam radiation for the management of patients with pancreatic cancer. One hundred eighty patients with biopsy-proven adenocarcinoma of the pancreas have been treated by a single surgical practice between 1979 and 1992. Of these, 105 had locally advanced but unresectable primary tumors (stages 2 and 3). All patients were treated with a program of multimodality therapy, including surgery, chemotherapy, and radiation therapy. Three groups were identified. Group I (33 patients) received intraoperative radiation therapy (IORT) as part of their treatment. Group II (43 patients) received intraoperative radiation in the form of iodine-125 (I-125) implantation. Group III (29 patients) received no intraoperative radiation. All three groups were comparably similar with respect to age at presentation, amount of preoperative weight loss, preoperative symptoms, and tumor location. Overall perioperative mortality was 4.8 per cent (five patients), with no difference between groups noted. Perioperative complications occurred in 32 (30.4%) of the 105 patients. Complications occurred in only 18.1 per cent of patients in Group I (IORT), compared with 39.5 per cent of Group II (I-125) patients (P < 0.01). Group III patients (no intraoperative radiation) experienced complications in 31.0 per cent of cases (P = 0.09 vs Group I). Actuarial survival was 18 months for Group I (IORT) versus 15 months for Group II (I-125). One- and 2-year actuarial survival rates were 60 and 17 per cent for patients in Group I (IORT) and 56 and 19 per cent for Group II (I-125). Actuarial local control rates for patients receiving IORT (Group I) was 70 per cent at 2 years. Patients with pancreatic cancer historically have poor survival and local control rates despite aggressive chemotherapy and radiation. The addition of intraoperative radiation to the combined modality management of pancreatic cancer offers markedly improved survival rates and local control with minimal morbidity for patients with unresectable disease. Intraoperative radiation in the form of IORT can be delivered with a significantly fewer complications than I-125 seed implantation.     

Recurrence and survival rate after surgical therapy of rectal carcinoma

Between 1983 and 1993, 680 patients with rectal carcinoma were treated at Ulm University. The resection rate was 84%. After undergoing radical surgery, 492 of the patients were followed up regularly at our hospital for a median of 66.9 months (range 4-177.6). Recurrences occurred in 172 patients (35%) and were diagnosed a median of 13 months (range 4-106 months) postoperatively; 9.4% had regional recurrences, 10.4% regional recurrences and distant metastases and 10.2% distant metastases. The 10-year survival rate of the patients in tumour stages I, II and III was 88%, 62%, and 32%. In patients with carcinoma of the midrectum, after anterior resection or abdominoperineal amputation the same local recurrence rate was found.     

Brief preoperative radiotherapy in surgical therapy of rectal carcinoma. Long-term results of a prospective randomized study

To ascertain whether preoperative short-term radiotherapy can improve local tumor control and the long-term survival of patients with operable rectal cancer, a prospective randomised trial was performed from 1988 to 1993. Ninety-three patients with rectal cancer were either directly treated with surgery (n = 46) or underwent preoperative radiotherapy with 5 x 3.3 Gy irradiation and operation within 48 h (n = 47). If indicated (T4, UICC stage III) patients also received postoperative irradiation. Comparison of the methods of operation (abdominoperineal amputation versus anterior resection) revealed no significant difference in 5-year survival rate (P = 0.393). Local control of R0-resected tumors was improved after preoperative irradiation (P = 0.08). The 5-year survival rate was significantly higher after preoperative short-term radiotherapy (P = 0.027). Preoperative radiotherapy is not an independent factor according to overall survival (P = 0.078) and local recurrence (P = 0.07). In agreement with the results of other authors the present study indicates improved local tumor control of rectal cancer after preoperative radiation therapy. The 5-year survival rate was significantly better after preoperative radiotherapy than after surgery alone.     

Molecular and pharmacological characterization of recombinant rat/mice N-methyl-D-aspartate receptor subtypes in the yeast Saccharomyces cerevisiae

PURPOSE: To assess the local control and survival in patients who received pelvic irradiation for locally recurrent rectal carcinoma. METHODS AND MATERIALS: The records of 519 patients with locally recurrent rectal carcinoma treated principally with external-beam radiation therapy between 1975 to 1985 at a single institute were retrospectively reviewed. These included 326 patients who relapsed locally following previous abdominoperineal resection, 151 after previous low anterior resection, and 42 after previous local excision or electrocoagulation for the primary. No patients had received adjuvant radiation therapy or chemotherapy for the primary disease. Concurrent extrapelvic distant metastases were found in 164 (32%) patients at local recurrence and, in the remaining 355, the relapse was confined to the pelvis. There were 290 men and 229 women whose age ranged from 23 to 91 years (median = 65). Median time from initial surgery to radiation therapy for local recurrence was 18 months (3-138 months). Radiation therapy was given with varying dose-fractionation schedules, total doses ranging from 4.4 to 65.0 Gy (median = 30 Gy) over 1 to 92 days (median = 22 days). For 214 patients who received a total dose > or = 35 Gy, radiation therapy was given in 1.8 to 2.5 Gy daily fractions. RESULTS: The median survival was 14 months and the median time to local disease progression was 5 months from date of pelvic irradiation. The 5-year survival was 5%, and the pelvic disease progression-free rate was 7%. Twelve patients remained alive and free of disease at 5 years after pelvic irradiation. Upon multivariate analysis, overall survival was positively correlated with ECOG performance status (p = 0.0001), absence of extrapelvic metastases (p = 0.0001), long intervals from initial surgery to radiation therapy for local recurrence (p = 0.0001), total radiation dose (p = 0.0001), and absence of obstructive uropathy (p = 0.0013). Pelvic disease progression-free rates were positively correlated with ECOG performance status (p = 0.0001), total radiation dose (p = 0.0001), and previous conservative surgery for the primary (p = 0.02). CONCLUSIONS: Survival is poor for patients who develop local recurrence following previous surgery for rectal carcinoma. Pelvic radiation therapy provides only short-term palliation, and future efforts should be directed to the use of effective adjuvant therapy for patients with rectal carcinoma who are at high risk of local recurrence.     

Successful retransplantation of mouse-to-rat cardiac xenografts under immunosuppressive monotherapy with cyclosporine

BACKGROUND: Total mesorectal excision (TME) is advocated for rectal cancer but the indications and extent of resection vary widely between surgeons. METHODS: Seventy-six consecutive patients (61 elective, 15 acute admission) with rectal or rectosigmoid cancer were admitted to a unit where TME was the preferred surgical option for potentially curative cancer at all levels of the rectum. RESULTS: Procedures undertaken were anterior resection (38 patients), abdominoperineal resection (18), Hartmann's procedure (ten) and transanal excision (one). Six patients had proximal faecal diversion alone and surgery was withheld in three. Anastomotic leaks occurred in six of 37 patients who had anterior resection with primary anastomosis, resulting in one early death. The presence of a proximal stoma did not influence the rate or seriousness of anastomotic dehiscence. After potentially curative TME in 45 patients, there have been eight local recurrences, four associated with systemic metastases and four which occurred in isolation (median follow-up 34 months). CONCLUSION: Curative TME was deemed appropriate in 59 per cent of unselected patients with rectal cancer. It was associated with few local recurrences but a morbidity rate that questions its role in treatment of upper third tumours.     

The role of neoadjuvant therapy in surgically resectable esophageal cancer

OBJECTIVE: To determine the effect of neoadjuvant therapy (NT) (preoperative chemotherapy, radiation therapy, or both) in surgically resectable esophageal cancer. DESIGN: A retrospective review over a 20-year period. SETTING: A tertiary academic medical center. PARTICIPANTS: All patients undergoing surgical resection for esophageal cancer (N = 316) over this time period. MAIN OUTCOME MEASURES: Perioperative morbidity and mortality, local and distant recurrences, and overall survival. RESULTS: Patients undergoing NT (n = 106) had prognostic factors similar to those treated with surgery alone (n = 210). No increase was noted in surgical morbidity with NT (anastomotic leaks, reoperation rates, complications, or extended hospital stays). Overall survival was not improved by NT (median survival, 14 months) except in the subset of patients (11/83) who responded completely (100% histological necrosis) to preoperative chemotherapy (median survival, 79.2 months; P < .02). Complete response to radiation therapy alone was not associated with improved survival. Partial necrosis of the primary tumor was seen in 13 (15%) of 83 patients but conferred no survival advantage. Complete response to preoperative chemotherapy was associated with squamous cell pathological features and excellent performance status as measured by preanesthesia evaluation. CONCLUSIONS: The addition of NT did not increase perioperative morbidity or mortality. Only the subset of patients who had a complete response to preoperative chemotherapy showed a survival advantage. Excellent performance status and squamous cell pathological features were associated with an increased chance of complete pathological response following preoperative chemotherapy.     

Patterns of recurrence following pelvic exenteration and external radiotherapy for locally advanced primary rectal adenocarcinoma

BACKGROUND: Local recurrence remains the main site of failure after pelvic exenteration for locally advanced primary rectal adenocarcinoma. This is a report on the patterns of recurrence in a group of such patients treated with pelvic exenteration and radiotherapy. METHODS: Between 1980 and 1992, we treated 49 patients. Thirty-one received preoperative radiotherapy (pre-RT), 4,500 cGy. Six weeks later, we performed posterior pelvic exenteration (PPE) in 21 patients, and total pelvic exenteration (TPE) in 10. Nine patients received postoperative radiotherapy (post-RT), 5,000 cGy after a PPE. Nine patients had surgery only, PPE (n = 7) and TPE (n = 2). RESULTS: Surgical mortality occurred in 16% of those patients who received pre-RT. The median follow-up was 52 months. Recurrences occurred in 23% of those patients who received pre-RT (local, one; local/distant, one; distant, four); in 88% of those patients treated with surgery only (local/distant, four; distant, four); and in 11% of those treated with post-RT (distant, one). The 5-year survival for patients who received radiotherapy was 66 versus 44% for those treated with surgery only. CONCLUSION: Local control of locally advanced primary rectal adenocarcinoma requiring a pelvic exenteration is improved by the addition of radiotherapy. When recurrences do occur they are predominantly at extrapelvic sites.     

Inhibition and activation of the thyroidal axis by the adrenal axis in vertebrates

PURPOSE: To determine the long-term effects of 75.6- and 81.0-Gy doses of three-dimensional conformal radiation therapy in a dose-escalation study in patients with stage T2c-T3 prostatic cancer. MATERIALS AND METHODS: Fifty patients received an initial 75.6-Gy dose, and the dose in 46 patients was subsequently escalated to 81.0-Gy. Median follow-up was 60 and 40 months, respectively. RESULTS: The rates of effects of acute toxicity during the course of treatment were similar for both dose levels. Among the 96 patients, the rate of grade 2 morbidities necessitating medication to relieve acute symptoms was 17% (16 patients) for rectal and 36% (35 patients) for urinary morbidities. All other patients had either no or grade 1 morbidities. Fourteen patients (15%) developed late grade 2 rectal morbidities. There were no differences in 5-year actuarial rates of late grade 2 rectal or urinary morbidities among patients who received 75.6 Gy versus those who received 81.0 Gy. One patient treated with 81.0 Gy developed a grade 3 urethral stricture, which was resolved with dilatation. CONCLUSION: Tumor dose escalation beyond conventional radiation doses for localized prostatic cancer is feasible when delivered with three-dimensional conformal radiation therapy, with no increase in morbidity in normal tissue.     

Local recurrence after simple mastectomy

A retrospective study was carried out to determine the clinical significance of local recurrence after simple mastectomy and node biopsy for primary operable breast cancer, without postoperative irradiation or systemic adjuvant therapy. Local recurrence was defined as a histologically proven lesion in or deep to the mastectomy skin flaps. A total of 966 patients with a median follow-up of 7 years were reviewed. Of these, 223 (23 per cent) developed local recurrence but half the tumours were small single lesions; 70 women had multiple discrete lesions and 21 diffuse carcinomatous dermal infiltration. Local recurrence showed significant associations with tumour grade, nodal status and the presence of lymphovascular invasion in the primary tumour. A predictive index containing these three variables was constructed. Adjuvant irradiation of the flaps is recommended for patients with high scores; such women would otherwise have a 39 per cent chance of developing local recurrence by 5 years. Different types of local recurrence have different chances of responding to local therapy: 13 per cent of single local recurrences, 32 per cent of multiple spot recurrences and 70 per cent of the diffuse type failed to respond to local therapy. Local recurrence predicts reduced patient survival.     

Stage T1-2 prostate cancer: a multivariate analysis of factors affecting biochemical and clinical failures after radical prostatectomy

PURPOSE: Prostate-specific antigen (PSA) is extensively used in case selection and outcome evaluation after treatment of clinically localized prostate cancer. Careful case selection can have a profound impact on pathologic findings and ultimate outcome. In addition, salvage treatment is frequently initiated at the time of biochemical relapse rather than clinical recurrence. Consequently, patterns of failure can be significantly altered compared to previous times when PSA was not available. To better understand the impact of PSA on pathologic findings, outcome, and salvage treatment, we reviewed our experience in the PSA era with clinical Stage T1-2 prostate cancer treated with radical prostatectomy. METHODS AND MATERIALS: Between 1987 and 1993, 423 cases could be identified with clinical Stage T1-2 prostate cancer treated with radical prostatectomy. The distribution of cases by pretreatment PSA levels was as follows: < or = 4 ng/ml (18%), 4-10 ng/ml (42%), 10-20 ng/ml (21%), > 20 ng/ml (14%), and unknown (5%). The median pretreatment PSA level for the entire group was 8.0 ng/ml. Sixteen patients received adjuvant or neoadjuvant androgen suppression and 13 received postoperative radiotherapy. Only 31 patients (7%) had pathologically positive pelvic lymph nodes. The overall margin involvement rate was 46%. Fifty-three percent of patients had surgical Gleason scores > or = 7, and 65% had extracapsular extension. The median follow-up time was 41 months. RESULTS: The projected overall survival at 7 years after surgery was 90%. The 5-year clinical relapse-free survival rate was 84%. At 5 years, the local control and distant failure rates were 92% and 91%, respectively. Biochemical relapse was defined as a detectable or rising PSA level after prostatectomy. The 5-year biochemical relapse-free survival (bRFS) rate was 59%. The 5-year RFS was 88% in patients with preoperative PSA levels < or = 4, 62% for 4-10, 48% for 10-20, and 31% for > 20. Combining the two independent preoperative variables, iPSA and biopsy GS (bGS), two risks groups were defined: low risk [initial PSA (iPSA) levels < or = 10.0 and bGS < or = 6] and high risk (iPSA levels > 10.0 ng/ml or bGS > or = 7). The 5-year bRFS rate for the low-risk cases was 81% vs. 40% for high-risk cases (p < 0.001). On multivariate analysis, three factors independently predicted biochemical relapse: iPSA levels (p = 0.005), Gleason score from the surgical specimen (sGS) (p = 0.002), and positive surgical margins (p < or = 0.001). The 5-year bRFS rates for margin positive vs. margin negative patients were 37% vs. 78%, respectively. The 5-year bRFS rates for GS > or = 7 vs. GS > or = 6 were 42% vs. 80%, respectively. All clinical relapses were accompanied by a rise in PSA. In patients who manifested biochemical failure followed by a clinical failure, the median interval between the PSA rise and clinical failure was 19 months (range 7-71). Margin involvement was the only independent predictor of local failure (p = 0.019). The 5-year local failure-free survival for negative margin cases was 96% vs. 87% for positive margin cases (p = 0.012). Lymph node (LN) involvement and high-risk group were the two independent predictors of distant failure. The 5-year distant failure-free survival for negative LN cases was 94% vs. 67% for positive LN cases (p < 0.001). The 5-year distant failure-free survival for low-risk cases was 97% vs. 85% for high-risk cases (p = 0.005). For the 124 patients failing biochemically, 85 were observed and 39 were treated either with radiation or androgen deprivation. With a median follow-up of 32 months, the clinical disease relapse-free survival was 79% for the treated patients vs. only 32% for the patients observed (p < 0.001). CONCLUSION: Pretreatment PSA is the most potent clinical factor independently predicting biochemical relapse, thereby allowing markedly better case selection. Achieving negative margins, even in relatively advanced disease, provides excellent lon     

Radiotherapy and local control in rectal cancer

Recurrence is a stage in the natural history of rectal cancer. Preoperative radiotherapy or postoperative radiochemotherapy lower the rate of recurrence, improving local control. From 1980 to 1997, at the "Divisione di Radioterapia" of the "Università Cattolica del S. Cuore" of Rome 380 patients with rectal cancer of early clinical stage T2-3, candidates for surgery for cure, underwent radiation therapy. 119 patients underwent postoperative radiotherapy (45-50 Gy); 45 patients underwent "sandwich" radiotherapy (45 Gy:27 Gy before and 28 Gy after surgery), of whom 7 were treated with preoperative radiotherapy alone; 145 patients underwent preoperative concomitant radiochemotherapy according to 3 different protocols, radiotherapy (38 Gy) combined with mitomycin C and 5-FU; radiotherapy (50.4 Gy) combined with cisplatin and 5-FU; radiotherapy (45 Gy) combined with 5-FU and folinic acid. 71 patients were treated with preoperative radiotherapy (38 Gy) combined with IORT (10 Gy). Median follow-up was 6 years. Overall local control was 85% at 3 years, 83% at 5 years, 81% at 10 years. The rate of local control at 5 years was: 76% for postoperative radiotherapy, 83% for "sandwich" radiotherapy, 84% for preoperative radiochemotherapy and 93% for preoperative radiotherapy combined with IORT. Local control was shown to be significantly better with preoperative treatment as compared to postoperative treatment (p = 0.02). The incidence of metastases was 35% in the patients with local recurrence and 16% in those with local control. The difference in survival was highly significant in patients with local control as compared to those with local recurrence: at 5 years 87% and 32% respectively. Patients with local control showed a lower incidence of metastasis and a better survival.     

Prognostic significance of histological type in gastric carcinoma with invasion confined to the stomach wall

Survival was determined after resection for the two main histological types of gastric carcinoma, intestinal (n = 223) and diffuse (n = 170), in 393 patients with pT1 or pT2 tumours. Lymph node metastases were present in 94 patients. The 10-year survival rate was significantly lower for patients with intestinal-type than for those with diffuse-type carcinoma (72 versus 91 per cent, P < 0.005). In patients without nodal involvement, the 10-year survival rate was still lower for those with intestinal-type cancer (70 versus 94 per cent, P < 0.01). Recurrence of carcinoma was more often by haematogenous dissemination in patients with intestinal-type cancer. Although the results of resection for pT1 or pT2 gastric carcinoma can be acceptable, the introduction of adjuvant therapy based on histological findings may be necessary for patients with the intestinal type of cancer to prevent haematogenous spread of carcinoma to the liver.     

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.     

Prognostic significance of lymph node dissection in gastric cancer

The results for 162 patients who underwent curative gastrectomy for gastric cancer from January 1988 to June 1994 were analysed statistically with special reference to the effect of lymph node dissection. Median survival was 69.3 months and the overall cumulative 5-year survival rate was 50.2 (95 per cent confidence interval (c.i.) 41.6-58.1) per cent. By univariate analysis age, histology, depth of tumour invasion, node involvement, number of metastatic lymph nodes and type of lymphadenectomy were found to be significant factors related to survival time. Multivariate analysis with the Cox model and stratified for tumour node metastasis stage revealed that only the number of metastatic nodes (P = 0.04) and the extent of lymphadenectomy (P = 0.003) affected survival independently. With respect to D1 lymphadenectomy, the relative risk associated with D2 and D4 lymphadenectomy was respectively 0.61 (95 per cent c.i. 0.34-1.10) and 0.26 (95 per cent c.i. 0.12-0.60). The 5-year survival rate was 28 per cent for patients who had a D1 dissection, 63 per cent for those who had D2 and 68 per cent for those who had D4. These results suggest that extended lymphadenectomy (D2) and especially superextended lymphadenectomy (D4) can improve survival in patients with gastric cancer.     

Microsporidia of the genus Trachipleistophora--causative agents of human microsporidiosis: description of Trachipleistophora anthropophthera n. sp. (Protozoa: Microsporidia)

Only limited data are available on chromosomes specifically involved in prostatic tumour progression. This study has evaluated the cytogenetic status of primary prostatic carcinomas, local tumour recurrences, and distant metastases, representing different time points in prostatic tumour progression. Interphase in situ hybridization (ISH) was applied with a set of (peri) centromeric DNA probes, specific for chromosomes 1, 7, 8 and Y, to routinely processed tissue sections of 73 tumour specimens from 32 patients. Longitudinal evaluation was possible in 11 cases with local recurrence and nine cases with distant metastases. The remaining 12 patients showed no evidence of local recurrence or distant metastasis after radical prostatectomy on follow-up (mean 60.5 months) and served as a reference. Numerical aberrations of at least one chromosome were found in 27 per cent of the local recurrences and 56 per cent of the distant metastases. In decreasing order of frequency, +8, +7, and -Y were observed in the recurrences and +8, +7, -Y, and +1 in the distant metastases. Evaluation of the corresponding primary tumour tissue of the recurrence group showed numerical aberrations in 45 per cent of cases. The aberrations found were, in decreasing order of frequency, -Y, +7, and +8. In the concomitant primary tumour tissue of the distant metastasis group, numerical aberrations were detected in 67 per cent of cases. The aberrations most frequently encountered were +8, -Y, followed by +7. In four cases, a concordance was found between the primary tumour and its recurrence or distant metastasis. Discrepancies might have been caused by cytogenetic heterogeneity. Comparison of the primary tumour tissue of the reference, the recurrence, and the distant metastasis groups showed a significant increase for the percentage of cases with numerical aberrations (Ptrend = 0.02). Likewise, a trend was seen for gain of chromosome 7 and/or 8 (Ptrend < 0.05). The number of DNA aneuploid tumours also increased in these different groups (Ptrend = 0.03). These data suggest that cancers which recur in time display an intermediate position between tumours of disease-free patients and metastatic cancers.     

Cerebral hemodynamics during implantation of cardioverter-defibrillator systems

PURPOSE: The prognosis of patients with pelvic wall recurrences after primary therapy of cervical cancer is bad. In selected patients treated exclusively by surgery as primary therapy the 5-year survival rate was between 5 and 25%. Additionally the combination of operation and radiotherapy (CORT) improved the survival so far. We developed a new concept for the treatment of pelvic wall recurrences. This concept includes the combination of radical surgery, interstitial radiation and chemotheray--CORCT (combined operative- and radiochemotherapy). PATIENTS AND METHODS: After radical surgery, interstitial HDR (Ir-192) brachytherapy in afterloading technique (2.5 Gy, 2 fractions/day in 5 days) was performed. Additionally a chemotherapy with cisplatin 25 mg/m2/day in 5 days and 5-fluorouracil 1000 mg/day in 5 days was applicated. RESULTS: After combined operative- and radiotherapy 3 of 3 patients died after treatment within 8 months (median) because of distant metastases. After additive radiochemotherapy 3 of 4 patients had no evidence of disease (NED) after a follow-up period of 14 (12 to 30) months. CONCLUSION: The first treatment results of the new designed combined operative- and radiochemotherapy concept (CORCT) led us to expect an improvement of the prognosis of patients with recurrences of cervical cancer at the pelvic wall.