The fate of patients with locally advanced bladder cancer treated conservatively with neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy: 10-year experience

PURPOSE: We assess the results of bladder preservation for infiltrating bladder cancer. The potential for neoadjuvant chemotherapy followed by extensive transurethral resection and radiotherapy was evaluated in 40 patients with T2-T4a G2-G3 bladder carcinoma. MATERIALS AND METHODS: From 1983 to 1995, 40 patients with bladder cancer underwent bladder sparing treatment, consisting of neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy. Most patients had T3G3 cancer. A deep transurethral resection biopsy was performed before and after chemotherapy, and an extensive transurethral resection was repeated at the end of radiotherapy. Of the patients 30 received cisplatin and methotrexate and 10 also received vinblastine. Total dose of radiotherapy was 60 to 65 Gy. Recurrent superficial tumors were treated transurethrally. Radical cystectomy was considered for persistent or recurrent invasive disease. RESULTS: Complete response occurred in 19 patients (47.5%) after chemotherapy, and in 8 patients after transurethral resection and radiotherapy (67.5%). Within 10 years 8 responding patients (30%) had local recurrences and 3 underwent cystectomy. Of the patients 14 (35%) are alive, including 13 with no evidence of disease (mean survival 65 months), 5 died of unrelated disease and 21 (52.5%) died of distant metastases (mean survival 28 months). Of the 21 patients 14 had residual tumor after radiotherapy, 3 presented with distant metastases after vesical infiltrating recurrence and 4 had distant metastases in the absence of locoregional recurrence. In 22 patients (55%) the bladder was salvaged. Patients with complete response to chemotherapy had a low risk for recurrent infiltrating tumors and metastases. CONCLUSIONS: Complete tumor control was maintained at 5 years in more than 50% of the patients treated conservatively. Bladder salvage is feasible in select patients.     

Anorectal melanoma--an incurable disease?

PURPOSE: This study was designed to describe recurrence and survival rates after operative treatment for anorectal melanoma and to identify predictive factors for recurrence. METHODS: Records of 50 patients with anorectal melanoma from 1939 to 1993 were reviewed. RESULTS: Overall five-year survival and disease-free survival were 22 and 16 percent, respectively. At the time of diagnosis, 26 percent of patients had metastatic disease, and all died within 12 (mean, 6.3) months. Five-year survival and recurrence rates were identical after either abdominoperineal resection (APR) or wide local excision, both with curative intent. Gender, size of tumor, presence of melanin, positive perirectal lymph nodes, or treatment were not predictive of recurrence. Anorectal melanoma was found incidentally after hemorrhoidectomy or polypectomy in five patients. Three other patients underwent an excisional biopsy of a lesion measuring less than 2 cm. Of these eight patients, five underwent APR and three underwent wide local excision with no microscopic residual tumor at pathology. All developed regional or systemic recurrence at a mean of 21 (range, 4-88) months, and all died of their disease at a mean of 29 (range, 5-98) months. CONCLUSION: Prognosis for anorectal melanoma is poor, irrespective of surgical treatment performed. No predictive factors for recurrence were identified in this series. Wide local excision with a negative margin of a least 1 cm is suggested as the treatment of choice. APR should be reserved for tumor not amenable to local excision or for palliative treatment of large obstructive lesion until effective adjuvant therapies are available.     

A review of the principles of pulse oximetry and accuracy of pulse oximeter estimates during exercise

OBJECTIVE: The outcomes of patients with squamous cell carcinoma of the anal canal treated by either sphincter-preserving procedures or radical surgery were evaluated, with the goals of identifying factors predicting treatment failure and quantifying results of salvage therapy in patients with recurrent disease. BASIC PROCEDURES: A population-based study on all patients in all 159 hospitals of the Department of Veterans Affairs (VA) from 1987 to 1991 was carried out. Data were compiled from several national computerized VA data sets. Supplementary information from local tumor registrars also was obtained, including demographic information, discharge summaries, operative reports, pathology reports, and medical oncology and radiation oncology summaries. From these sources, information on tumor histology, tumor stage, tumor grade, presence of regional or distant metastases, surgical procedures, use of chemotherapy and radiation therapy (RT), toxicity of chemotherapy and RT, development of recurrent disease, treatment of recurrence, survival, and cause of death were obtained. MAIN FINDINGS: Four hundred five patients with anal cancer were identified by computer search, and 204 (51%) were evaluable; 164 of 204 (80%) had squamous cell carcinoma, 137 of whom (84%) were treated with sphincter-preserving procedures, and 27 of whom (16%) were treated by by radical surgery. One hundred fourteen of 138 (83%) were treated by multimodality therapy, which we defined as local excision followed by chemotherapy and RT. The mean dose of RT among patients treated by multimodality therapy was 4200 +/- 540 cGy and 82% of those treated with multimodality therapy received 5-FU/mitomycin C. Recurrent disease was diagnosed in 43 of all 149 patients (29%) with potentially curable disease. (stages I-III) Multivariate analysis revealed that stage at diagnosis (p = 0.04) and method of treatment (p = 0.03) were the sole predictors of recurrence. Fifty-three percent of patients who underwent salvage abdominoperineal resection (APR) are alive, whereas only 19% who underwent salvage chemotherapy with or without RT are alive. PRINCIPAL CONCLUSIONS: These data indicate that multimodality therapy currently is being employed in the majority of patients with squamous cell carcinoma of the anal canal in the VA system. Tumor stage and method of treatment appear to affect the likelihood of development of recurrent disease. Salvage APR has curative potential. Results with salvage chemotherapy and RT are disappointing.     

The role of squamous cell carcinoma antigen in the management of laryngeal and hypopharyngeal cancer

BACKGROUND: The efficacy of squamous cell carcinoma antigen (SCC-Ag) in laryngeal cancer to predict those patients who will relapse after primary treatment (surgery or radiotherapy) and its utility to detect relapses early and thereby increase salvage rates and cure were assessed. METHODS: Sixty healthy donors and 168 patients with laryngeal cancer were included in this prospective trial. Squamous cell carcinoma antigen was measured at diagnosis in all patients, 24 hours and 1 week after surgery in 113 patients and every 10 Gy of administered dose and 2 weeks after treatment in 49 patients primarily referred to radiotherapy. The marker was determined every 3-6 months during follow-up. All patients who relapsed had SCC-Ag studies before and after salvage treatment. RESULTS: The selected cut-off value was 1.5 ngr/ml (mean value in control group, 0.65 + 2 standard deviation [0.38]). Seventy-eight percent of patients with cancer had elevated SCC-Ag values at diagnosis. Squamous cell carcinoma antigen was statistically related to TNM categories (T, P < 0.04; N, P < 0.05; Stage, P < 0.01). Seventy-five percent of those patients with previously elevated pretreatment values normalized after treatment. Incomplete surgical resection (P < 0.0001) or persistence of the disease after radiotherapy (P < 0.01) were related to high posttreatment values. Squamous cell carcinoma antigen was elevated in 88% of the patients who relapsed. In 55% of the recurrences, SCC-Ag was elevated 3 months before pathologic confirmation of relapse. Salvage by surgery or radiotherapy was effective in 70% of the patients. Squamous cell carcinoma antigen posttreatment values were the most important factor in predicting disease free survival (DFS) (P < 0.0001) and overall survival (P < 0.03). CONCLUSIONS: Squamous cell carcinoma antigen is an excellent marker of residual disease after primary treatment that can lead to the addition of other therapeutic procedures (surgery and postoperative radiotherapy). The absence of posttreatment SCC-Ag is the best predictor of DFS, its presence detects recurrence in early stages, permitting salvage of an increased proportion of patients primarily referred for palliative treatment.     

Management of carcinoma anal canal with combination chemotherapy and concurrent radiotherapy

Results of 21 cases of squamous cell carcinoma of anal canal treated by continuous infusion of 5-fluorouracil 1000 mg/sqm for 4 days and mitomycin-C 15 mg/sqm on 1st day by i.v. route with concurrent external beam radiotherapy of 42 Gy from 1st day of chemotherapy were analysed. Out of 21 patients, 16(76.19%) achieved complete remission, 3 (14.28%) partial remission and 2 (9.52%) cases did not respond at all. On follow-up, 7 (33.33%) histopathological positive cases needed abdominoperineal resection with good recovery. After 2 years of follow-up 14 (66.67%) cases were free from the disease and 3 (14.28%) were alive with the disease. The median duration of follow-up was 36 months.     

Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial

CONTEXT: For the treatment of a single metastasis to the brain, surgical resection combined with postoperative radiotherapy is more effective than treatment with radiotherapy alone. However, the efficacy of postoperative radiotherapy after complete surgical resection has not been established. OBJECTIVE: To determine if postoperative radiotherapy resulted in improved neurologic control of disease and increased survival. DESIGN: Multicenter, randomized, parallel group trial. SETTING: University-affiliated cancer treatment facilities. PATIENTS: Ninety-five patients who had single metastases to the brain that were treated with complete surgical resections (as verified by postoperative magnetic resonance imaging) between September 1989 and November 1997 were entered into the study. INTERVENTIONS: Patients were randomly assigned to treatment with postoperative whole-brain radiotherapy (radiotherapy group, 49 patients) or no further treatment (observation group, 46 patients) for the brain metastasis, with median follow-up of 48 weeks and 43 weeks, respectively. MAIN OUTCOME MEASURES: The primary end point was recurrence of tumor in the brain; secondary end points were length of survival, cause of death, and preservation of ability to function independently. RESULTS: Recurrence of tumor anywhere in the brain was less frequent in the radiotherapy group than in the observation group (9 [18%] of 49 vs 32 [70%] of 46; P<.001). Postoperative radiotherapy prevented brain recurrence at the site of the original metastasis (5 [10%] of 49 vs 21 [46%] of 46; P<.001) and at other sites in the brain (7 [14%] of 49 vs 17 [37%] of 46; P<.01). Patients in the radiotherapy group were less likely to die of neurologic causes than patients in the observation group (6 [14%] of 43 who died vs 17 [44%] of 39; P=.003). There was no significant difference between the 2 groups in overall length of survival or the length of time that patients remained functionally independent. CONCLUSIONS: Patients with cancer and single metastases to the brain who receive treatment with surgical resection and postoperative radiotherapy have fewer recurrences of cancer in the brain and are less likely to die of neurologic causes than similar patients treated with surgical resection alone.     

Effectiveness of mastectomy by response to induction chemotherapy for control in inflammatory breast carcinoma

BACKGROUND: Controversy exists as to the treatment regimen necessary to best provide optimal local control for inflammatory breast carcinoma (IBC). This study was conducted to determine if mastectomy combined with radiotherapy offered any advantages over radiotherapy alone in patients with IBC who had been treated with doxorubicin-based combination chemotherapy. METHODS: A retrospective review of 178 women treated for IBC on doxorubicin-based multimodality therapy protocols between January 1974 and September 1993 was performed. Clinical and histologic response to treatment, time to local recurrence, survival, and ultimate control of local disease were analyzed. Kaplan-Meier analysis was used to examine survival and relapse times, and Fisher's exact test was used to test differences in treatment outcomes. Significance was determined at p < or = 0.05. RESULTS: Median follow-up was 89 months (range 22 to 223 months). Locoregional disease persisted in seven patients and recurred in 44 patients who had been rendered disease free at a median time of 10 months. The mortality rate after a local recurrence (LR) was 98%, and all patients but one with LR developed systemic metastases. Response to induction chemotherapy influenced the incidence of LR, and the amount of residual disease found on histologic examination of mastectomy specimens was highly prognostic for local failure. Patients who underwent mastectomy in addition to radiotherapy had a lower incidence of LR than did patients who received radiotherapy alone (16.3% vs. 35.7%, p = 0.015). CONCLUSIONS: The addition of mastectomy to combination chemotherapy plus radiotherapy improved local control in patients with IBC. The addition of mastectomy to chemotherapy plus radiotherapy improved distant disease-free and overall survival in patients with a clinical complete or partial response to induction chemotherapy. Patients who had no significant response to induction chemotherapy received no survival or local disease-control benefit from the addition of mastectomy to their treatment regimen. These patients should be considered for entry into clinical trials of new treatment regimens.     

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.     

Completion right lower lobectomy for recurrence after left pneumonectomy for metastases

Resection of pulmonary recurrences on the residual lung after pneumonectomy for metastases is exceptional. A 37-year-old woman was submitted to left extended pleuro-pneumonectomy after left leg amputation for fibrosarcoma. At 43 months later, a wedge resection on the right lower lobe was performed followed 32 months later by a further wedge resection in the same lobe. A completion right lower lobectomy for a new recurrence was performed 17 months after the last pulmonary resection. The patient did not develop postoperative complications. She is still alive and free of disease 10 years and 9 months after pneumonectomy and 36 months after completion lobectomy on the residual lung. In highly selected patients, aggressive surgery for metastases on the residual lung can be successfully performed and it can improve survival.     

Primary chemoradiation therapy with fluorouracil and cisplatin for cancer of the anus: results in 35 consecutive patients

PURPOSE: This prospective phase II study was designed to test the activity and toxicity of a regimen of fluorouracil (5-FU) and cisplatin (CDDP) in combination with radiation therapy in the treatment of epidermoid cancer of the anal canal. PATIENTS AND METHODS: Thirty-five consecutive patients with untreated epidermoid cancer of the anal canal were candidates for chemoradiation therapy (CRT). Staging of cancer was as follows: T1, 26%; T2, 60%; T3, 14%; and N1, 2,3, 26%. No patient had distant metastases. The treatment protocol consisted of two to three cycles of chemotherapy starting on days 1 and 21 and concurrent radiotherapy at a daily dose of 1.8 Gy up to a total dose of 36 to 38 Gy in 4 weeks, delivered to the anal region, perineum, middle and lower pelvis, and inguinal and external iliac nodes. Radiotherapy was then delivered to the anoperineal region and metastatic inguinal nodes to a total dose of 18 to 24 Gy in 10 fractions. Chemotherapy consisted of 24-hour intravenous (IV) infusion of 5-FU 750 mg/m2 on days 1 to 4 and CDDP 100 mg/m2 by 60-minute IV infusion on day 1. RESULTS: All patients received two cycles of chemotherapy; the second was delayed in three patients because of leukopenia that was evident in 11 (31%). In eight patients, a third cycle was added. They all experienced nausea or vomiting; one patient showed signs of cardiotoxicity and one developed proctitis, dermatitis, and diarrhea (grade 3). Complete regression (CR) was assessed in 33 patients (94%); nine patients with metastatic lymph nodes also had CR. Two patients had a partial response (PR); both underwent abdominoperineal resection, which was not curative in one. Two patients (6%) had a local recurrence; in one, this was associated with hepatic metastases. One of these patients underwent surgery and is alive after about 4 years, while the other is undergoing chemotherapy. After a median follow-up duration of 37 months, 94% of patients are alive without evidence of disease and 86% are colostomy-free. CONCLUSION: This regimen is well tolerated; its toxicity does not exceed that observed with the combination of 5-FU and mitomycin (MMC). Compared with our previous experience based on the classic CRT (5-FU, MMC, and radiation), the objective response rate observed with this new combination was similar. However, the local recurrence rate, observed in patients treated with the new regimen, was lower (6% v 24%). According to more recent data from the literature, primary CRT is the elective indication in epidermoid cancer of the anus and replacement of MMC with CDDP seems an effective and logical evolution.     

Locally advanced primary colorectal cancer: intraoperative electron and external beam irradiation +/- 5-FU

PURPOSE: For locally advanced primary colorectal cancer, our institution has combined intraoperative electron irradiation (IOERT) with external beam irradiation (EBRT) +/- 5-fluorouracil (5-FU) and surgical resection. Disease control and survival were compared with the current IOERT and prior non-IOERT regimens. METHODS AND MATERIALS: From April 1981 through August 1995, 61 patients received an IOERT dose of 10-20 Gy, usually combined with 45-55 Gy of fractionated EBRT; 56 had minimum follow-up of 18 months. The amount of residual disease remaining at IOERT after exploration and maximal resection in the 56 patients was gross in 16, < or = microscopic in 39, and unresected in 1. RESULTS: Survival (SR) and disease control were analyzed as a function of potential prognostic factors. Factors that achieved statistical significance for improved overall survival included treatment sequence of preop EBRT + 5-FU (vs. postoperative EBRT + 5-FU, p = 0.003) and < or = microscopic residual disease after maximal resection (vs. gross residual, p = 0.005). Those that appeared to favorably impact disease-free survival included EBRT + 5-FU (vs. EBRT alone, p = 0.01), < or = microscopic residual (vs. gross, p = 0.0014), and colon site of primary (vs. rectum, p = 0.009). Failures within an irradiation field have occurred in 4 of 16 patients (25%) who presented with gross residual after partial resection vs. 2 of 39 (5%) with < or = microscopic residual after gross total resection (p = 0.01). The significant prognostic factors for a decrease in distant metastases were the same as for disease-free SR with respective p-values of 0.013 (EBRT + 5-FU), 0.008 (microscopic residual), and 0.03 (colon primary). The current data suggests a relationship between IOERT dose and incidence of Grade 2 or 3 neuropathy (< or = 12.5 Gy--1 of 29 or 3%, > or = 15 Gy--6 of 26 or 23%, p = 0.03). CONCLUSIONS: Both overall survival and disease control appear to be improved with the addition of IOERT to standard treatment. More routine use of systemic therapy is indicated as a component of IOERT containing treatment regimens because the incidence of distant metastases was 50% of patients at risk.     

Prognostic features of teratomas with malignant transformation: a clinicopathological study of 21 cases

PURPOSE: Teratomas with malignant transformation comprise up to 6% of metastatic teratomas. The prognosis of patients with these tumors can vary considerably. We delineate factors that may be related to prognosis in a cohort of men with teratoma with malignant transformation. MATERIALS AND METHODS: We analyzed pathological features, treatment, response, recurrence, time to recurrence, subsequent followup and survival for 21 patients (median age 28 years) diagnosed with teratoma with malignant transformation during a 7-year period at our institution. RESULTS: Malignant nongerm cell elements were present in the primary tumor in 11 cases (52%). Of 18 patients with testicular primaries 17 (94%) presented with metastatic disease. Despite aggressive treatment with surgery and chemotherapy 17 of 21 cases (81%) recurred (median time 6 months). Overall, 5 patients (24%) died of disease (median survival 23 months), 5 (24%) are alive with metastases (median followup 41 months) and 11 (52%) have no evidence of disease (median followup 50 months). Progression/recurrence was substantially greater for 2 of 2 cases with a mediastinal origin, 3 of 4 with rhabdomyosarcomatous differentiation and 5 of 6 with neural differentiation compared with the remainder of the cohort (p < 0.05). CONCLUSIONS: Teratomas with malignant transformation are usually metastatic at presentation, have a high recurrence rate and are more aggressive than teratomas without malignant transformation. Prognosis is especially poor for mediastinal teratomas with malignant transformation and for those with neural or rhabdomyosarcomatous differentiation. Complete surgical resection of residual or recurrent disease appears to offer the best chance for prolonged survival.     

Blood-flow sensing by anionic biopolymers

The purpose of this study was to compare local recurrence, distant metastases, and survival rate in 350 patients with cancer of the middle and low rectum who underwent a radical abdominoperineal resection (APER) or a sphincter-saving resection (SSR) in our Institute. There were 257 APER patients and 93 SSR patients, with a median follow-up of 77 months. At 5 years, the estimates in APER and SSR patients were respectively 11% and 30% for the incidence of pelvic recurrence, 18% and 8% for the incidence of distant metastases, and 64% and 73% for overall survival. In the multivariate analysis it was found that Dukes' stage significantly affected pelvic recurrences, distant metastases rate and overall survival; histologic type affected only the pelvic recurrence rate. However, the final outcome of patients following APER or SSR was similar, suggesting that local failure per se does not affect long-term survival.     

Surgical results for spinal metastases

Among a series of 740 spinal tumours treated in the Department of Neurosurgery at the Nordstadt Hospital in Hannover, Germany, between September 1977 and December 1996, 106 spinal metastases in 101 patients were operated on. After an average period of 4.0 +/- 6 months (2 days to 5 years) patients presented at an average age of 62 +/- 12 years. 79% of the tumours were operated on by a posterolateral approach, 12% by an anterior and the remaining 9% by an anterior and posterior approach. A complete resection was achieved for 43.4% of the metastases while 48.1% were removed partially, 7.5% were biopsied and one patient received an opiate pump. Operations were followed by radiotherapy, chemotherapy or hormone treatment. The overall local recurrence rates as determined by the Kaplan Meier method were 57.9% after 6 months, 69.3% after 1 year and 96% after 4 years. Multiple regression analyses revealed that an independent preoperative status of ambulation, favourable tumour histology, cervical level, complete resection, low number of affected vertebral bodies, and elective surgery were significant, independent predictors of a low rate of local metastatic recurrence. Postoperative neurological outcome was related to preoperative neurological deficits. 96% of patients walking preoperatively kept this ability for at least 3 months postoperatively. However, only 22% of patients unable to walk regained walking capacity for 3 months. Correspondingly, 89% of patients remained continent of urine postoperatively for 3 months while only 31% regained sphincter control for this amount of time postoperatively. In terms of postoperative survival, multiple regression analyses showed longer survival times for patients with a favourable tumour histology, independent ambulation, long history, male sex, cervical level, complete resection, posterior approach, no additional metastases in other organs, and no instability. The overall survival rates were 58.8% after 6 months, 48% after 1 year and 19.5% after 5 years postoperatively. In conclusion, surgery has a place in the treatment of patients with metastatic disease of the spine and neurological symptoms and/or spinal instability. The surgical strategy should be tailored according to the general health of the patient and expected time of survival. Primary radiotherapy should be administered to patients without neurological deficits or instability and to patients who cannot undergo or do not accept surgery.     

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.     

Radiotherapy after chemotherapy for metastatic seminoma--a diminishing role. MRC Testicular Tumour Working Party

In a retrospective study, data from 302 patients with metastatic testicular seminoma treated with chemotherapy between 1978 and 1990 in 10 European centres were analysed to evaluate the role, if any, of postchemotherapy treatment with irradiation. The primary endpoint of this study was the progression-free survival rate after chemotherapy with or without additional radiotherapy. This was related to the type of primary chemotherapy, sites and sizes of pre- and postchemotherapy masses, the extent of surgical resection after chemotherapy and the use of radiotherapy. 174 patients had residual disease at the end of chemotherapy. The most important prognostic factors for progression were the presence of any visceral metastases or raised LDH prechemotherapy, and the presence of residual disease at visceral sites after chemotherapy. Approximately half the patients with residual masses underwent postchemotherapy radiotherapy, with selection based predominantly on institutional practice. In patients receiving platinum-based chemotherapy, no significant difference was detected in progression-free survival whether or not radiotherapy was employed. Patients receiving BEP (bleomycin, etoposide and cisplatin) had a progression-free survival rate of 88% (95% CI, 80-96%) uninfluenced by postchemotherapy radiotherapy. In patients with residual masses confined to the abdomen after platinum-based chemotherapy, the absolute benefit to radiotherapy was estimated to be 2.3%. The potential benefit of postchemotherapy radiotherapy is minimal, and so it is concluded that the use of adjuvant radiotherapy to residual masses after platinum-based chemotherapy for metastatic seminoma is unnecessary.     

Carcinoma of the extrahepatic bile ducts. The University of California at San Francisco experience

OBJECTIVE: The authors investigated the combined experience of a single institution in treating bile duct carcinoma during the modern era. SUMMARY BACKGROUND DATA: Bile duct carcinomas are notoriously difficult to cure, with locoregional recurrence the rule, even after radical resection. Adjuvant efforts have included various radiation modalities, with limited success. Recently, charged-particle radiotherapy has also been used in these patients. METHODS: The authors performed a retrospective chart analysis of 129 patients with bile duct adenocarcinomas treated between 1977 and 1987 through the University of California at San Francisco, including 22 patients treated at Lawrence Berkeley Laboratory with the charged particles helium and neon. The minimum follow-up was 5 years. Survival, outcome, and complication results were analyzed. RESULTS: Sixty-two patients were treated with surgery alone (S), 45 patients received conventional adjuvant x-ray radiotherapy (S + X), and 22 were treated with charged particles (S + CP). The median survival times were 6.5, 11, and 14 months, respectively, for the entire group, and 16, 16, and 23 months in patients treated with curative intent. There was a survival difference in patients undergoing total resection compared with debulking (p = 0.05) and minor resections (p = 0.0001). Patients with microscopic residual disease had increased median survival times when they were treated with adjuvant irradiation, most markedly after CP (p = 0.0005) but also with conventional X (p = 0.0109). Patients with gross residual disease had a less marked but still statistically significant extended survival (p = 0.05 for S + X and p = 0.0423 for S + CP) after irradiatio CONCLUSIONS: The mainstay of bile duct carcinoma management was maximal surgical resection in these patients. Postoperative radiotherapy gave patients with positive microscopic margins a significant survival advantage and may be of value in selected patients with gross disease.     

Viruses and atherosclerosis: do they play a pathogenic role?

PURPOSE: To evaluate the results of interstitial radiotherapy of anorectal tumors. PATIENTS AND METHODS: From 1972 to 1993, one of the authors treated 45 patients by an interstitial implant for anorectal tumors. Of these, 33 patients suffered from primary tumors, 19 from squamous carcinoma, 2 from basaloid carcinoma of the anus and the other 12 from primary adenocarcinoma of the rectum. Of 12 patients treated for local recurrence, 10 had adenocarcinoma and 2 squamous cell carcinoma. Of the 33 patients with primary tumors, 27 received a course of external-beam radiotherapy before the implant. The median follow-up was 35 months. RESULTS: Local response depended on the tumor volume treated. All 21 anal tumors showed complete response, 5 patients developed local recurrence and 4 distant metastases: 3 died from their disease. Of 12 rectal adenocarcinomas, 9 responded completely, 4 patients developed local recurrence and 4 distant metastases; 6 died from active disease. In the last group of 12 patients who were treated for recurrent tumors, 7 responded completely. One patient developed local recurrence and 9 distant metastases, only 4 are alive. CONCLUSIONS: A combination of external-beam and interstitial radiotherapy is a relatively simple, non-mutilating, but well-tolerated and very effective method of treatment for early carcinoma of the lower rectum and anus.     

Identification of autolysosomes directly associated with proteolysis on the density gradients in isolated rat hepatocytes

BACKGROUND: More than 40% of patients who undergo curative resection of advanced colorectal carcinoma can be expected to have recurrence of the disease. The most frequent sites of recurrence are the liver (33% of patients) and lung (22%). Interest has therefore focused on treating hepatic or pulmonary metastases, or both, to improve the outcomes of these patients. Although surgical resection has become an increasingly accepted treatment for resectable localized hepatic or localized pulmonary metastases from colorectal carcinoma, the value of aggressive surgery for the removal of both hepatic and pulmonary metastases from patients with primary colorectal carcinoma remains to be clarified. METHODS: Data on 30 patients who had undergone resection of both hepatic and pulmonary metastases from colorectal carcinoma were included in the study. RESULTS: Independent, significant prognostic features were found to be the time that hepatic or pulmonary metastases occurred and the distribution of pulmonary metastases. Median survival times were 30 months (range, 7-108 months) after resection of both hepatic and pulmonary metastases and 48.5 months (range, 11-149 months) after excision of the primary colorectal tumor. Actuarial 1-, 3-, and 5-year survival after resection of both hepatic and pulmonary metastases was 86.7%, 49.3%, and 43.8%, respectively. No perioperative mortality occurred. There were three cases of minor morbidity, which the authors considered acceptable. CONCLUSIONS: Resection of both hepatic and pulmonary metastases from colorectal carcinoma may help to prolong the survival of a small group of patients with these metastases.     

Free revascularized jejunal loop repair following total pharyngolaryngectomy for carcinoma of the hypopharynx: report of 90 patients

Ninety patients with carcinoma of the hypopharynx underwent pharyngolaryngectomy and reconstruction with a jejunal free autograft. Fifty-five patients had primary surgery and 35 salvage surgery for recurrence after radiotherapy. Following primary surgery 28 patients had postoperative radiotherapy and 27 did not. Complications occurred in 51 per cent of patients, the most common being necrosis of the jejunal graft (19 per cent); 12 per cent developed significant stenosis and 4 per cent died in the perioperative period. Eleven per cent of patients developed a fistula. The total number of complications diminished as the experience of the unit increased. Median follow-up was 4.9 years. Of patients treated with primary surgery, 48 per cent developed primary site recurrence (at 3 years) and 53 per cent neck node recurrence (at 5 years). The tumour-specific 5-year survival rate for all patients was 42 per cent. Following primary surgery 28 per cent survived for 5 years and after salvage surgery the rate was 59 per cent. Positive resection margins and extensive neck disease adversely affected survival (P = 0.02 and P = 0.001 respectively). The free revascularized jejunal graft is a safe and predictable method of repair following total pharyngolaryngectomy.