Carcinoma of the tonsillar fossa: prognostic factors and long-term therapy outcome

PURPOSE: To identify prognostic parameters and evaluate the therapeutic outcomes for patients with carcinoma of the tonsillar fossa treated with three treatment modalities. METHODS AND MATERIALS: The results of therapy are reported in 384 patients with histologically proven epidermoid carcinoma of the tonsillar fossa; 154 were treated with irradiation alone (55-70 Gy), 144 with preoperative radiation therapy (20-40 Gy), and 86 with postoperative irradiation (50-60 Gy). The operation in all but four patients in the last two groups consisted of an en bloc radical tonsillectomy with ipsilateral lymph node dissection. RESULTS: Treatment modality and total irradiation doses had no impact on survival. Actuarial 10-year disease-free survival rates were 65% for patients with T1 tumors, 60% for T2, 60% for T3, and 30% for T4 disease. Patients with no cervical lymphadenopathy or with a small metastatic lymph node (N1) had better disease-free survival (60% and 70%, respectively) at 5 years than those with large or fixed lymph nodes (30%). Primary tumor recurrence (local, marginal) rates in the T1, T2, and T3 groups were 20-25% in patients treated with irradiation and surgery and 31% for those treated with irradiation alone (difference not statistically significant). In patients with T4 disease treated with surgery and postoperative irradiation, the local failure rate was 32% compared with 86% with low-dose preoperative irradiation and 47% with irradiation alone (p = 0.03). The overall recurrence rates in the neck were 10% for N0 patients, 25% for N1 and N2, and 35-40% for patients with N3 cervical lymph nodes, without significant differences among the various treatment groups. The incidence of contralateral neck recurrences was 8% with the various treatment modalities. On multivariate analysis the only significant factors for local tumor control and disease-free survival were T and N stage (p = 0.04-0.001). Fatal complications were noted in 7 of 144 (5%) patients treated with preoperative irradiation and surgery, 2 of 86 (2%) of those receiving postoperative irradiation, and 2 of 154 (1.3%) patients treated with radiation therapy alone. Other moderate or severe nonfatal sequelae were noted in 30% of the patients treated with preoperative irradiation and surgery, in 53% treated with postoperative irradiation, and in 19% receiving radiation therapy alone. CONCLUSION: Primary tumor and neck node stage are the only significant prognostic factors influencing locoregional tumor control and disease-free survival. Treatment modality had no significant impact on outcome. Radiation therapy remains the treatment of choice for patients with stage T1-T2 carcinoma of the tonsillar fossa. In patients with T3-T4 tumors and good general condition, combination surgery and postoperative irradiation offers better tumor control than single-modality and preoperative irradiation procedures, but with greater morbidity.     

Radical hysterectomy with pelvic lymphadenectomy in patients with carcinoma of the uterine cervix--3 years' experience

INTRODUCTION: Almost all patients with invasive cervical carcinoma can be treated with either primary irradiation therapy or primary surgery. Some patients are appropriately treated with the combination of irradiation and surgery. Chemotherapy is not effective as primary treatment of invasive cervical cancer but may be used as additional therapy and when the disease is recurrent or persistent. There are some important advantages of primary extensive surgery over irradiation. The findings at operation and that from the careful pathologic examination of surgical specimens can be very helpful in selection of patients for supplementary postoperation irradiation therapy or chemotherapy, or both [1-6]. AIM OF THE STUDY: The aim of the study was to compare pretreatment clinical evaluations with surgical and postsurgical pathohistological findings. METHODS: Extensive hysterectomy and bilateral pelvic lymphadenectomy were used in the treatment of 251 patients with early invasive cervical cancer. The patients were treated at the Department of Obstetrics and Gynaecology of the Clinical Centre of Serbia in Belgrade, between 1993 and 1995. Cervical cancer was detected by clinical examination, colposcopic and cytologic (Pap smear) findings, colposcopically directed biopsy or conisation and pathological findings, sonography, chest radiography, blood and urine analyses. In some cases we had to make other examinations (cystography, cystoscopy, intravenous pyelography, sygmoidoscopy, rectoscopy, CT scanning and magnetic resonance). The surgical treatment of invasive carcinoma of the cervix was limited to those patients in whom the disease was confined to the cervix or vaginal fornix (stage Ia, stage Ib or stage IIa), and who were in high surgical risk. RESULTS: Over a three year period (1993-1995) there were 251 patients with invasive cervical cancer, treated by primary surgery (radical hysterectomy and bilateral pelvic lymphadenectomy sec. Werthein-Meigs), average age 42 years. Most of the patients demonstrated invasive cervical cancer, clinically classified in Ib st. (81.67%). Some characteristics of pathologic findings, such as parametric width, number of removed lymph nodes, percentage of lymph nodes metastases and correlation with clinical stage of invasive cervical cancer, histologic grade of cervical cancer with lymph node metastasis, pathologic findings after surgical treatment, correlation between clinical and surgical staging, were already presented in tables. DISCUSSION: In the last decades the incidence of invasive cervical cancer and death rate have been decreased. Progress in reducing mortality is primarily attributed to the introduction of cervical cancer screening as part of regular gynaecologic examinations. Regular testing with Papanicolaou (Pap) smear and colposcopy have an important role in this problem [1]. Extensive hysterectomy and bilateral pelvic lymphadenectomy were used in the treatment of 251 patients with early invasive cervical cancer. We found that the clinical diagnosis of disease extent was correct in 67.7% of patients who underwent extensive surgery for early invasive cervical cancer. Sensitivity of clinical findings was 75.8% and positive predictive value was 86.2%. Lymph node metastasis was detected in 17% patients. Brodman at al. [14] found that clinical examinations, including CT scanning and magnetic resonance, were correct in only 62.5% of cases. It is very difficult to detect parametric involvement and lymph node metastasis by clinical examinations. Irradiation therapy was used in the postoperative period as additional treatment of extensive hysterectomy and bilateral pelvic lymphadenectomy in 89.7% of patients. CONCLUSION: The findings at operation and that from the careful pathologic examination of surgical specimens are absolutely irreplaceable and important in grading invasive cervical cancer and selection of patients for supplementary postoperate irradiation therapy.     

Contrasting effects of an aminobisphosphonate, a potent inhibitor of bone resorption, on lipopolysaccharide-induced production of interleukin-1 and tumour necrosis factor alpha in mice

PURPOSE: To evaluate whether transient androgen deprivation improves outcome in patients irradiated after radical prostatectomy for locally advanced disease, persistent or rising postoperative prostate specific antigen (PSA), or local recurrence. METHODS AND MATERIALS: Records of 105 consecutive patients who were treated with pelvic irradiation after radical retropubic prostatectomy between August 1985 and December 1995 were reviewed. Seventy-four patients received radiation alone (mean follow up: 4.6 years), and 31 received transient androgen blockade with a gonadotropin-releasing hormone agonist (4) androgen receptor blocker (1) or both (24) beginning 2 months prior to irradiation (mean follow-up 3.0 years) for a mean duration of 6 months. Two of these patients were excluded from further analysis because they received hormonal therapy for more than 1 year. Patients received a prostatic fossa dose of 60-70 Gy at 2 Gy per fraction; 48 patients also received pelvic nodal irradiation to a median dose of 50 Gy. Survival, freedom from clinical relapse (FFCR), and freedom from biochemical relapse (FFBR) were evaluated by the Kaplan-Meier method. Biochemical relapse was defined as two consecutive PSA measurements exceeding 0.07 ng/ml. RESULTS: At 5 years after irradiation, actuarial survival for all patients was 92%, FFCR was 77%, and FFBR was 34%. FFBR was significantly better among patients who received transient androgen blockade before and during radiotherapy than among those treated with radiation alone (56 vs. 27% at 5 years, p = 0.004). FFCR was also superior for the combined treatment group (100 vs. 70% at 5 years, p = 0.014). Potential clinical prognostic factors before irradiation did not differ significantly between treatment groups, including tumor stage, summed Gleason histologic score, lymph node status, indication for treatment, and PSA levels before surgery or subsequent treatment. Multivariate analysis revealed that transient androgen deprivation was the only significant predictor for biochemical failure. CONCLUSION: This retrospective study of irradiation after radical prostatectomy suggests that transient androgen blockade and irradiation may improve freedom from early biochemical and clinically evident relapse compared to radiotherapy alone, although more prolonged follow-up will be needed to assess durability of impact upon clinical recurrence and survival rates.     

A long-term assessment of adjuvant chemotherapy on outcome of patients with extracapsular spread of cervical metastases from squamous carcinoma of the head and neck

BACKGROUND: Extracapsular spread (ECS) of cervical lymph node metastases of squamous cell carcinoma from head and neck sites portend poor prognosis. Therefore, a program of combined surgery, postoperative irradiation therapy, and adjuvant methotrexate and 5-fluorouracil (5-FU) was initiated in 1982 for such patients. METHOD: All patients operated on between June 1982 and December 1992 by the full-time faculty of the Department of Otolaryngology at the University of Pittsburgh School of Medicine were eligible and reported in this trial. All patients had negative surgical margins of excision of the primary carcinoma, and histologic evidence of cervical metastases with ECS. Postoperative irradiation included 50-60 cGy for 5 to 6 weeks followed by methotrexate and 5-FU administered on an outpatient basis on days 1 and 8 every 21 days. All patients were followed for 30 or more months for evidence of recurrent disease. RESULT: A total of 371 patients met eligibility criteria. Of this group, 53 (14%) were treated with surgery only, 187 (50%) received surgery and postoperative irradiation, and 131 (35%) received surgery, irradiation therapy, and chemotherapy. The primary site, extent of nodal involvement, and stage of the three patient groups were similar. However, performance status (Karnofsky) was best in the patients who received chemoradiation (average 90) when compared with those who received surgery and irradiation (average 80) or surgery only (average 70). Absolute disease free survival rate (30 months) was 9.5% in patients treated with surgery only, 34% in patients treated with surgery plus irradiation, and 53% in patients treated with surgery, irradiation, and chemotherapy. When adjusted for patients who died of intercurrent disease with less than 30 months follow-up, survival rates became 17%, 40%, and 58%, respectively. These differences are highly significant (P < 0.001). CONCLUSION: Results of this study suggest that postoperative chemoradiation may improve survival in patients with ECS of cervical metastases. Compliance with the chemoradiation was suboptimal and suggests that improved strategy must be developed.     

The role of cell communication in the pathogenesis of breast cancer]

OBJECTIVE: The aim of the study is to analyse long-term results of patients with small cell lung cancer (SCLC) treated at the same institution according to a prospective study including surgery, chemotherapy, and radiotherapy. METHODS: From 1981 to 1995, 104 patients with a proven histology of SCLC underwent surgery, chemotherapy, and radiotherapy. Fifty-one patients with operable stage I or II lesion received surgical resection followed by adjuvant chemotherapy and radiotherapy. Fifty-three patients with proved SCLC and clinical stage III received induction chemotherapy followed by surgery and radiotherapy. All patients received from four to six courses of chemotherapy and 36 had prophylactic cranial irradiation (PCI). All patients had follow-up for at least 1 year, and survival time was calculated from the date of the diagnosis until death or most recent follow-up. RESULTS: Ninety-six patients were male and eight female. We performed 29 pneumonectomies, eight bilobectomies, 66 lobectomies and one no resection. Regarding the clinical stage, 35 patients (33.6%) had stage I, 16 patients (15.4%) had stage II and 53 (51%) had stage III. Post-operative pathologic staging revealed stage I in 37 patients (35.6%), stage II in nine patients (8.6%), stage III in 45 patients (43.3%), and in 13 patients (12.5%) there was no more tumor. The 30-day mortality was 2% (two patients). Fourteen patients (13.4%) had post-operative complications. Fifty-one patients (49%) had a relapse. The median follow-up was 55 months. Twenty-six patients remain alive and 78 patients have died. The overall 5-year survival rate was 32%, with an estimate median survival time of 28 months; according to the pathologic stage, the survival data were 52.2%, 30% and 15.3% for stage I, II and III, respectively (P < 0.001). The 5-year survival was 41% in patients without SCLC after chemotherapy. CONCLUSION: As with non-small cell lung cancer, survival following surgery and chemotherapy clearly correlates with the stage. At present, it is not clear whether surgery is truly effective for patients with SCLC. In our experience, the complete elimination of small cell lung cancer is associated with an improvement in survival (41% at 5 years).     

The management of deeply infiltrating (T3) bladder carcinoma: controlled trial of radical radiotherapy versus preoperative radiotherapy and radical cystectomy (first report)

The preliminary results are presented of a multicentre, co-operative randomised trial, sponsored by the Institute of Urology, London, in which radical irradiation (6,000 rads in 6 weeks) is compared with preoperative irradiation (4,000 rads in 4 weeks) plus radical cystectomy for deeply infiltrating carcinoma of the bladder (Stage T3 or B2C). 189 of the 199 cases entered into the trial between 1966 and 1975 were eligible for study. The overall 3- and 5-year survival rates for combined treatment were 41% and 33%, respectively, compared with 28% and 21% for radical radiotherapy. The operative mortality was 7.8%. The difference between the two treatments in favour of the combined treatment has not yet reached the generally accepted level of significance (P less than 0.05), the p factors for the 3- and 5-year results being 0.064 and 0.077, respectively. Of patients receiving the protocol combined treatment, reduction in tumour stage was found in the surgical specimen in 47% of cases. The overall incidence of nodal metastases was 23% (against the usual figure of 40-50%), and in the presence of a good response of the primary tumour to irradiation, only 8%. The 3- and 5-year survival rates for the down-staged cases were 66% and 55%, respectively, compared with 29% and 22% for patients showing no stage reduction in the surgical specimen. The aim of our future studies is to find effective radiosensitising and cytotoxic agents with which to try and increase the incidence and degree of tumour response to pre-operative irradiation in the combined modality treatment of T3 bladder cancers.     

Radical vulvectomy with postoperative irradiation for vulvar cancer: therapeutic implications of a central block

PURPOSE/OBJECTIVE: To report the long-term results of vulvectomy, node dissection, and postoperative nodal irradiation using a midline vulvar block in patients with node positive vulvar cancer. METHODS AND MATERIALS: From 1971 through 1992, 27 patients with carcinoma of the vulva and histologically involved inguinal lymph nodes were treated postoperatively with radiation therapy after radical vulvectomy and bilateral lymphadenectomy (n = 25), radical vulvectomy and unilateral lymphadenectomy (n = 1), or hemivulvectomy and bilateral lymphadenectomy (n = 1). Federation Internationale de Gynecologic et d'Obstetrique stages were III (n = 14), IVA (n = 8), and IVB (n = 5) squamous cell carcinoma. Inguinal lymph nodes were involved with tumor in all patients (average number positive = 4, range 1-15). Postoperative irradiation was directed at the bilateral groin and pelvic nodes (n = 19), unilateral groin and pelvic nodes (n = 6), or unilateral groin only (n = 1). These 26 patients had the midline blocked. In addition, one patient received irradiation to the entire pelvis and perineum. Doses ranged from 10.8 to 50.7 Gy (median 45.5) with all patients except 1 receiving > or = 42.0 Gy. RESULTS: Actuarial 5-year overall survival and disease-free survival estimates were 40% and 35%, respectively. Recurrences developed in 63% (17/27) of the patients at a median of 9 months from surgery (range 3 months to 6 years) and 15 of these have died; two patients with recurrences are surviving at 24 and 96 months after further surgery and radiation therapy. Central recurrences (under the midline block) were present in 13 of these 17 patients (76%), either as central only (n = 8), central and regional (n = 4), or central and distant (n = 1). Additionally, three patients developed regional recurrences and one patient developed a concurrent regional and distant relapse. One patient developed a squamous cell cancer of the anus under the midline block 54 months after the initial vulvar cancer and an additional patient developed transitional cell carcinoma of the ureter (outside the radiation field) 12 months after diagnosis. Factors associated with a decreased relapse-free survival included increasing Federation Internationale de Gynecologic et d'Obstetrique stage (p = 0.01) and invasion of the tumor into the subcutaneous (SC) fat or deep soft tissue (p = 0.05). Chronic lower extremity edema developed in four patients, but there have been no other complications. CONCLUSIONS: Radical vulvectomy has often been considered sufficient central treatment for vulvar carcinoma, with postoperative irradiation directed only to the nodes. Although designed to protect the radiosensitive vulva, use of a midline block in this series resulted in a 48% (13/27) central recurrence rate, much higher than the 8.5% rate previously reported with this technique. Routine use of the midline block should be abandoned and, instead, postoperative irradiation volumes should be tailored to the individual patient.     

Soft tissue sarcomas: preoperative versus postoperative radiotherapy

External beam radiation may be given either before or after excision of a primary soft tissue sarcoma. This study was undertaken to determine whether or not the timing of radiotherapy was associated with any difference in either local control, survival, or incidence of complications. The files of 112 patients with a primary, nonmetastatic, extremity soft tissue sarcoma, treated with limb salvage surgery and irradiation were evaluated. Data regarding tumor stage, grade, site, surgical margin, dosage and timing of radiotherapy, treatment complications, disease relapse, and relapse-free survival (RFS) were analyzed. Kaplan-Meier lifetable analysis was used to determine survival estimates. There was no significant difference in the 5-year RFS between patients receiving radiotherapy (RT) preoperatively versus postoperatively; 56 +/- 15% and 67 +/- 12% (P = 0.12, Mantel-Cox), respectively. There was no significant difference in the overall survival between patients receiving RT preoperatively versus postoperatively; 75 +/- 15% and 79 +/- 11% (P = 0.94), respectively. Actuarial local control at 5 years for preoperative versus postoperative RT patients was not statistically different; 83 +/- 12% versus 91 +/- 8% (P = 0.41), respectively. Wound complications were more frequent in preoperative RT patients (31%) compared to postoperative RT patients (8%) (P = 0.0014, chi-square). Preoperative irradiation was not associated with any benefit in terms of relapse-free survival, overall survival or actuarial local control in this series. A higher incidence of major wound complications was found among patients treated with preoperative irradiation. We recommend that patients with a resectable extremity soft tissue sarcoma be treated with postoperative irradiation, reserving preoperative irradiation for those situations in which either the tumor is initially thought to be unresectable or the original tumor boundaries are obscured.     

Massive hemorrhage caused by a perforating Gianturco-Z stent resulting in an aortoesophageal fistula

Squamous cell carcinoma of the tonsil has a relatively poor prognosis. Aggressive surgery, radiation therapy and combinations of irradiation and surgery have been employed but there exists some controversy about the efficacy of these treatment modalities. The purpose of this paper is to compare the efficacy of treatment between the surgery followed by radiation therapy and the preoperative radiation therapy followed by surgical resection. The medical records of 33 patients treated for squamous cell carcinoma of the tonsil at the Department of Otolaryngology-Head and Neck Surgery, Korea University Hospital between 1989-1993 were reviewed retrospectively. None of the patients were stage I, but stage II, III, and IV were four, five, and 24 patients, respectively. There were 30 males and three females. The most common histopathology was moderately differentiated squamous cell carcinoma (20/33). The 13 patients treated initially with surgery had an overall three-year survival rate of 38.5%, and the rate for the 20 patients treated initially with radiation was 40%. The main pattern of treatment failure was a local recurrence and neck metastases, and pathologic differentiation thought to be an important prognostic factor. Complications are fewer in patients treated initially with surgery (23.1%) than patients initially treated with radiation (50.0%). There is no difference in the efficacy between the two therapeutic groups.     

Successful treatment of solitary extracranial metastases from non-small cell lung cancer

BACKGROUND: Recurrence after resection of non-small cell lung carcinoma is generally associated with a poor outcome and is treated with either systemic agents or palliative irradiation. Recently, long-term survival has been reported after resection of isolated brain metastases from non-small cell lung carcinoma, but resection of other metastatic sites has not been explored fully. METHODS: We have identified 14 patients who had solitary extracranial metastases treated aggressively after curative treatment of their non-small cell lung carcinoma. The histology was squamous carcinoma in 5, adenocarcinoma in 8, and large cell carcinoma in 1. Initially, 3 patients had stage I, 5 stage II, and 6 stage IIIa disease. RESULTS: The sites of metastases included extrathoracic lymph nodes (six), skeletal muscle (four), bone (three), and small bowel (one). The median disease-free interval before metastases was 19.5 months (range, 5 to 71 months). Complete surgical resection of the metastatic site was the treatment in 12 of 14 patients. Two patients received only curative irradiation to the metastatic site, with complete response. The overall 10-year actuarial survival (Kaplan-Meier) was 86%. To date, 11 patients are alive and well after treatment of their metastases (17 months to 13 years), 1 has recurrent disease, 1 died of recurrent widespread metastases, and 2 died of unrelated causes. CONCLUSION: Long-term survival is possible after treatment of isolated metastases to various sites from non-small cell lung carcinoma, but patient selection is critical.     

Exhumation and no end. A comparative analysis]

INTRODUCTION: In the last 25 years, random trials on the advantages of combined surgery and irradiation/chemotherapy of breast cancer demonstrated similar survival rates to those of massive surgery. However, both irradiation and chemotherapy have advanced and now yield good local control of the disease, so that even large breast cancers can be made operable. Breast cancer follow-up is carried out with imaging and clinical examinations to detect early locoregional recurrences, contralateral lesions and distant recurrences: to this purpose, we carried out a comparative study of all imaging modalities. MATERIAL AND METHODS: We retrospectively reviewed the data of 42 breast cancer (T2-T3 N0-N+) patients of the Senology Center of the Catholic University (Rome, Italy) treated with irradiation and/or chemotherapy for tumor debulking to permit conservative surgery. We investigated the sensitivity and the indications of mammography, B-mode and color Doppler US and MRI in measuring the exact tumor size and detecting locoregional metastatic nodes. RESULTS: After 3 years' treatment, our recurrence rate (19%) is a little higher than those in the major international trials (4.2-9% and 5 tears). The recurrence was on the surgical scar in 75% of cases (6/8), while multifocal tumors were found in 25% of cases. US was the most accurate method in measuring tumor size in 90% of cases (18/20), while mammography frequently overstaged the lesion and yielded exact measurements in 65% of cases (13/20). MRI was as accurate as US, but this technique is too expensive and little available in Italy. US accurately diagnosed lymph node recurrences (70% sensitivity), but MR rate was even higher (80%), while mammography and color Doppler US had only 5-10%. As for treatment outcome, an irregular and blurred nodule or multifocal lesions at mammography indicate poor/no response, while a much smaller radial scar than at previous similar follow-ups indicates treatment success. CONCLUSIONS: When correctly integrated, mammographic, US and MR patterns permit exact tumor size measurement and show possible locoregional lymph node involvement in the patients submitted to conservative surgery and irradiation/chemotherapy. In contrast, color Doppler findings remain poorly specific in this disease, with about 55% sensitivity. Therefore, radiologic studies, with clinical and laboratory data, have a major prognostic value in assessing the biological response to combined treatment.     

Mitochondrial DNA in idiopathic cardiomyopathy

143 women treated in 28 departments from 1980 to 1995 were retrospectively analysed to study the impact of prognostic factors in primary carcinoma of the fallopian tube. The mean age of the patients was 62.5 years. Sixty (42%) tumours were FIGO stage I, 28 (20%) stage II, 38 (27%) stage III, 17 (12%) stage IV. Complete radical resection was achieved in 102 (71%) patients. In 122 (85%) women, surgery involved removal of the uterus, the adnexa, and/or the omentum or lymph nodes. Postoperative therapy consisted of either irradiation (n = 40; 28%) or chemotherapy (n = 70; 49%); 33 women (23%) did not receive any treatment after surgery. The 5-year survival rate for all cases was 43%. The 5-year survival rate was 59% for stages I and II and 19% for stages III and IV (P < 0.00001). FIGO stage, histological grade and presence of residual tumour had an independent prognostic impact in multivariate analysis. In order to investigate the role of p53 in primary fallopian tube carcinomas, we analysed the immunohistochemical expression of p53 protein regarding survival and FIGO stage in 63 patients (44%). No statistical significance was observed.     

Analysis of prognostic factors in localized gastric lymphoma: the importance of bulk of disease

PURPOSE: To identify prognostic factors in localized gastric lymphoma patients for optimal therapy selection. METHODS AND MATERIALS: From 1974 to 1990, 77 patients with localized gastric lymphoma (38 Stage IE and 39 Stage IIE) were treated with radiation therapy, chemotherapy, surgery, or a combination. Univariate and multivariate local control and survival analyses were performed on possible prognostic factors, such as patient age, gender, histologic subtype, stage, tumor size, depth of penetration, multicentricity, and treatment modality. RESULTS: At 5 years, the relapse-free survival was 52%; 74% of the relapses occurred at local sites. Smaller tumor size was most strongly associated with local control (p = .001) and relapse-free survival (p < .001). Patients with tumor sizes < or = 5 cm had relapse-free survival of 87%, compared with 41% and 15% for those with tumor sizes of 5.1 cm to 10 cm and > 10 cm, respectively. The 47 patients who received combined-modality therapy had a relapse-free survival of 65%, compared with 24% for the 30 who received single-modality therapy (p < .01). Although patient age, stage, depth of penetration, and resective surgery affected the above endpoints, these factors were not independent predictors of outcome. Analysis of treatment subgroups showed that surgical resection combined with postoperative irradiation was associated with highest local control (p = .002) and the best relapse-free survival (p = .004), when compared with other treatment modalities. In 27 patients with tumor sizes < or = 5 cm, comparison of the 15 patients who had surgery with the 12 who did not failed to reveal a local control benefit from the addition of surgery. CONCLUSION: These data demonstrate that tumor bulk is an important prognostic determinant of local control and relapse-free survival in localized gastric lymphoma patients. Stage IE and IIE lymphoma of the stomach can be selectively treated with primary radiation, but surgical resection may be necessary for large tumors (> 5 cm), followed by adjuvant radiation.     

Studies on the phototoxic effects of oral antidiabetics and diuretics

Combined chemoradiotherapy (CT/RT) treatments appear to yield better results for advanced tumours of the head and neck than do conventional therapies. In the present study, CT/RT was used preoperatively in unresectable tumors of the oral cavity and oropharynx. Forty patients were entered prospectively into a phase II study. Treatment consisted of three cycles of chemotherapy with cisplatin and 5-day infusion of fluorouracil (FU), and the addition of simultaneous radiotherapy (30 Gy) from the second to third cycles. Patients with resectable residual disease or complete clinical response underwent surgery. All patients later received a second phase of irradiation (30 Gy) and two cycles of chemotherapy only in responders. During the first phase of treatment, 22 (55%) patients presented mucositis grades III-IV. Mean weight loss was 7%. Twelve patients were admitted for parenteral nutrition. Thirty-six (90%) patients obtained clinical response, which was complete in 15 (37%). Thirty-two of the 40 underwent surgery. The percentage of pathologic complete responses (PCR) was 35% (14 patients). With a median follow-up of 21 months, the median survival of patients was 23 months, and 19 (47%) of them are disease-free. A high PCR rate was attained with this treatment regimen. Toxicity was significant, but tolerable with adequate support measures.     

Treatment policy for maxillary sinus carcinoma

Some 908 cases of malignant tumors of the nose and paranasal sinuses treated from 1957 through 1974 were statistically analysed. The most common tumor site was the maxillary sinus (91.4%) and the most common histological figure was carcinoma (92.4%). The crude and relative survival rates for each treatment mode were calculated in January 1975. The number of cases and the 5 year relative survival rates of the main groups were as follows: I. Primary cases of malignant tumors (761 cases) 29.2% A. Carcinoma (709 cases) 29.3% B. Sarcoma (45 cases) 27.4% II. Primary cases of maxillary sinus carcinoma (561 cases) 26.1% A. Period 1957-66 (282 cases) 22.8% 1. Combination of irradiation and surgery (114 cases) 36.9% 2. Irradiation alone (168 cases) 12.7% B. Period 1967-69 (130 cases) 34.5% 1. Irradiation with 5-FU intra-arterial infusion (25 cases) 36.1% 2. Irradiation with intra-arterial infusion of other radiosensitizers (35 cases) 35.7% 3. Irradiation only without infusion (45 cases) 35.2% C. Period 1970-71, Linac X-ray irradiation (61 cases) 15.9% D. Period 1972-73, Irradiation with 5-FU infusion (80 cases), 3 year relative survival rate 39.3% The stage-grouping of maxillary sinus carcinoma based on the classification of tumor spread in the TNM system was recommended for the comparison of survival rates. The best mode of treatment in our experience is the combination of Co-60 gamma-ray irradiation and continuous intrarterial infusion of 5-FU. A curettage during irradiation is recommended. A maxillectomy should be performed only for irradiation failure cases.     

Squamous cell carcinoma of the thoracic esophagus following radiation therapy for breast cancer

Between 1981 and 1995, 4 patients (3 females, 1 male; aged 48-80) were diagnosed with squamous cell carcinoma of the esophagus, following mediastinal irradiation for breast cancer. The interval between irradiation and the presentation of esophageal cancer was 10.75 years on average (7-19). The treatment consisted of: radiotherapy only; a partial esophagectomy with proximal gastrectomy without post-operative radiotherapy; laser photocoagulation for a superficial tumor; and, palliative treatment including gastrostomy, tracheal photocoagulation and chemotherapy for 1 patient suffering from advanced stage cancer with tracheal invasion, respectively. Radiotherapy of the esophageal cancer (exclusive or adjuvant) should take into account previous esophageal radiation therapy. The indications of curative excision surgery are the same as for other types of esophageal cancer, but the anastomoses should be performed in a non-irradiated area. Excision by esophageal stripping without thoracotomy is contraindicated because of the presence of peri-esophageal sclerosis. Preventive measures in radiation therapy for breast cancer are suggested.     

High-dose rate intracavitary irradiation for carcinoma of the uterine cervix. The adverse effect of treatment prolongation

AIM: To investigate the adverse effect of treatment prolongation on the local control and survival of the cervical carcinoma of the uterus. PATIENTS AND METHOD: Two hundred and sixteen patients with stage IIB and III cervical carcinoma treated with a combination of external radiation and high-dose rate (HDR) intracavitary irradiation between 1978 and 1989 were retrospectively studied. A multivariate analysis was used to determine the effect of treatment time on local control and survival. RESULTS: Overall treatment time was the most highly significant factors for local control in the multivariate analysis (p = 0.0005). The 5-year cumulative relapse rates were significantly different with the treatment times 35 to 42 days: 9% versus 43 to 49 days: 19% versus 50 to 62 days: 42% (p = 0.001). The second most significant parameter was stage classification (p = 0.02). Concerning relapse-free survival, stage classification (p = 0.0001), overall treatment time (p = 0.0035) and hemoglobin level (p = 0.0174) were the 3 most important prognostic factors, although there was no relationship between treatment time and late complications. CONCLUSION: These results suggest that prolongation of treatment time is associated with decreased local control and survival in patients treated with external radiation and HDR intracavitary irradiation.     

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.     

Extensive polymorphism of the FUT2 gene in an African (Xhosa) population of South Africa

OBJECTIVE: Nephroureterectomy is the standard treatment for tumors of the renal pelvis and ureter. Conservative management or indication of adjuvant treatment in these neoplasms is based mainly in histological grade and stage. The aim of this study is to assess the relation of Ki67 index with other established prognostic factors and to define its predictive value for long term survival, which could be useful in selecting the best treatment for each individual case. METHODS: 81 patients with urothelial tumors of the renal pelvis and ureter, diagnosed and treated between 1975 and 1993, comprised the present study. Ki67 immunostaining was performed in paraffin-embedded tissue. A cut-off limit of 20% was chosen. Tumor location, histological grade, histological pattern, local (T), nodal (N), vascular and perineural invasion and stage (TNM) were assessed in relation to the proliferation index and as prognostic criteria for survival in both univariate and multivariate analysis. RESULTS: The Ki67 proliferation index was found to be related to grade (p < 0.001), T (T0 vs T1-4; p < 0.01), N (p < 0.038), TNM categories (stage 0 vs I-IV; p < 0.048) and perineural invasion (p < 0.01). There was a marginal relation to vascular invasion (p < 0.11). Survival was better for the patients with low proliferating tumors (90%) than for high proliferating ones (67%) (p < 0.02). In the multivariate analysis only T stage was statistically significant (p < 0.01) but a highly suggestive trend was found for the Ki67 index (p < 0.07). CONCLUSIONS: Tumor proliferation assessed by Ki67 immunostaining is related to the progression of the disease and proved to be of predictive value for long-term survival in tumors of the renal pelvis and ureter. The Ki67 index is able to detect high-risk patients that could not be cured by radical surgery alone, raising the need for some type of aduvant treatment in these cases. The treatment predictive effect observed in low grade-low stage cases suggests its possible utility in patients managed conservatively.     

Treatment of undeveloped external intestinal fistulas

135 patients with undeveloped intestinal fistulas (116-85.9%-males, and 19-14.1%-females) were followed up by the authors. The patients underwent surgery for acute appendicitis-17 (12.6%), traumatic injuries of abdominal organs-78 (57.8%), acute intestinal obstruction-33 (24.4%), inflammatory processes of the uterus and adnexites-7 (5.2%). Small bowel fistulas were observed in 88 (65.2%) of patients, large bowel fistulas-in 47 (34.8%). The optimal mode of treatment for the fistula seems the obturation of fistula duct by means of catheter of Petzer of Foley. It is guite necessary to perform a simultaneous broad exploration of abscesses of anterior abdominal wall and their sanatation by the method of flowing-aspiration therapy by N.N. Kanshin. For elimination of endotoxicosis the ultraviolet irradiation of autologous blood was used as well as intravenous laser irradiation of blood, hemosorption, plasmapheresis, infusions of plasma and plasma substitutional solutions. The patients were given 2-3 antibiotics of a broad spectrum of action, one of which being obligatory introduced intravenously. From 135 patients 104 (77.0%) underwent surgery. The method of choice in small bowel fistulas the authors suggest intraabdominal resection of the bowel, and in large bowel fistulas-resection of 3/4 by the method of A.V. Melnikov. 17 patients (17.3%) died after the surgery.