Combined chemotherapy and radiotherapy, followed or not by surgery, in squamous cell carcinoma of the esophagus

BACKGROUND: This study was designed to evaluate the feasibility of a neo-adjuvant combined chemo-radiotherapy in patients with localized squamous cell carcinoma of the esophagus. PATIENTS AND METHODS: Forty-two patients with squamous cell carcinoma of the esophagus, stages II and III (or stage I if considered to be poor candidates for immediate curative surgery), age less than 70 years and WHO performance status 0 to 2, were enrolled in a study of radiotherapy combined with chemotherapy, consisting of 2 (operated patients) or 3 (nonoperated patients) courses of cisplatin, vindesine, mitomycin-C or cisplatin, vinblastine. Surgery was routinely proposed to patients. RESULTS: Thirty-seven patients (88%) received full preoperative therapy. Of 30 patients responding to this preoperative therapy, 12 had a third cycle of treatment and 15 had esophagectomy. Three of the operated patients had no pathological evidence of residual tumour. Median survival of all 42 patients is 11 months and the 2-year survival rate is 29%. There is no difference in survival among responding operated or non-operated patients. Our group represents 95% of all eligible cases of squamous cell carcinoma of the esophagus occurring in Geneva during the study period. CONCLUSION: Our series gives a realistic view of the median survival of a population of patients eligible for neo-adjuvant therapy of esophagus cancer, and suggests that secondary surgery might not improve the patient survival. Furthermore, non-selected patients are at high risk for therapy-related death.     

Survival of patients with carcinoma of the esophagus treated with combined-modality therapy

Since 1985, 229 cases of carcinoma of the esophagus have been considered for entry into a protocol with the use of preoperative chemotherapy and radiation therapy followed by surgical intervention as the primary element of treatment. One hundred sixty-five patients (93 with adenocarcinoma and 72 with squamous cell carcinoma) had esophagogastrectomy. The 5-year survival of the protocol patients who underwent resection was 25% for both groups--squamous cell carcinoma and adenocarcinoma. Of the protocol patients with squamous cell carcinoma who underwent resection, 40% had a sterilized specimen, whereas of those with adenocarcinoma, 20% had a sterilized specimen. If the patient had a sterilized specimen, the 5-year survival was approximately 60% for adenocarcinoma and 40% for squamous cell carcinoma. Those patients with adenocarcinoma and Barrett's esophagus had a 5-year survival of 55%. Of the patients who underwent only esophagectomy and esophagogastrectomy and had not been entered into the protocol, none lived beyond 3 years. The operative mortality rate for those who had esophagogastrectomy was 5%. Sixty-four patients completed the radiation therapy and chemotherapy but did not undergo surgical procedures because of progressive disease or refusal. Of those patients who completed chemotherapy and radiation therapy without surgical intervention, 5-year survival was 18% in patients with squamous cell carcinoma, whereas no patients with adenocarcinoma survived beyond 3 years. The finding of a sterilized specimen after esophagectomy is a favorable prognostic factor in patients with adenocarcinoma or squamous cell carcinoma. The finding that patients with Barrett's esophagus and adenocarcinoma have an improved chance for survival is perhaps related to an earlier diagnosis. It is clear that some patients with squamous cell carcinoma who did not undergo surgical procedures did have a sterilized specimen, because the survival in this group approached 20% at 5 years.     

Neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy or surgery for operable thoracic esophageal carcinoma

PURPOSE: A prospective clinical trial was undertaken to investigate the feasibility of concurrent chemoradiotherapy for esophageal carcinomas. MATERIALS AND METHODS: Between June 1989 and May 1996, forty patients with operable squamous cell carcinoma of the thoracic esophagus (Stage 0 to III: UICC 1987), ages 45 to 78 years (mean: 64), were enrolled in a study of neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy (CRT group) or surgery (CRT-S group). Neoadjuvant chemoradiotherapy consisted of 44 Gy in 40 fractions for 4 weeks (2.2 Gy/2 Fr/day) through 10-MVX rays, with 2 courses of cisplatin (80-100 mg/body, mean: 60 mg/m2, Day 1, bolus injection) and 5-fluorouracil (500-1000 mg/body/day, mean: 400 mg/m2, Days 1-4, continuous infusion). After completion of neoadjuvant chemoradiotherapy, an intermediate clinical response was assessed by barium swallow, esophagoscopy with/without biopsy, EUS in most cases, thoracic and upper abdominal CT scan, and cervical US. Definitive chemoradiotherapy was performed in patients when regression of more than 75% was evident (CRT Group), and esophageal resection was indicated in those who remained at less than 75% (CRT-S Group). In CRT Group, a cumulative dose of 60-70 Gy for Tis, T1 and 65-75 Gy for T2-T4 tumor with high-dose-rate intraluminal brachytherapy and a total of 3 courses of chemotherapy were planned. In CRT-S Group, intraoperative radiotherapy for abdominal lymphatic system and postoperative supraclavicular irradiation were added. RESULTS: At the time of intermediate assessment, complete response (CR) was observed in 16 patients, a partial response (PR) in 22, and no change (NC) in 2. Thirty responding patients (CR, 16; PR, 14) entered the CRT Group, and 10 nonresponding patients (PR, 8; NC, 2) were followed by surgery (CRT-S Group). Radiotherapy was completed satisfactorily, but chemotherapy was suspended in 26 patients (65%) because of acute toxicity. Clinical CR rate at the completion of treatment showed 90% in CRT Group, and pathologic CR rate 10% in CRT-S Group. The overall median survival was 45 months, survival at 1, 2, and 3 years being 100%, 72%, and 56%, respectively. Local-regional failure was observed in 7 patients (all in CRT Group), distant failure in 6 (3 in CRT Group, 3 in CRT-S Group) and local-regional with distant failure in 1 (CRT Group). Four patients with local-regional recurrence in the CRT Group were salvaged by surgery. Overall survival at 2 and 3 years for CRT vs. CRT-S Group was 72%, 64% vs. 75%, 38%, respectively. No treatment-related mortality was observed. The rate of the 'esophagus conservation' was 65% (Stage 0: 1 of 1, 100%; Stage I: 11 of 12, 92%; Stage II: 8 of 17, 47%; Stage III: 6 of 10, 60%). CONCLUSION: Our results demonstrated that almost all early disease (Stage 0-I) and about half of advanced disease (Stage II-III) could be conserved, their esophagus treated by the multidisciplinary approach centering on high-dose radiotherapy and concurrent chemotherapy.     

Copper/zinc superoxide dismutase transgenic brain accumulates hydrogen peroxide after perinatal hypoxia ischemia

OBJECTIVE: This study aims to evaluate the risk of esophagectomy in the elderly compared with younger patients and to determine whether results of esophagectomy in the elderly have improved in recent years. SUMMARY BACKGROUND DATA: An increased life expectancy has led to more elderly patients presenting with carcinoma of the esophagus in recent years. Esophagectomy for carcinoma of the esophagus is associated with significant morbidity and mortality, and advanced age is often considered a relative contraindication to esophagectomy despite advances in modern surgical practice. METHODS: The perioperative outcome and long-term survival of 167 elderly patients (70 years or more) with esophagectomy for carcinoma of the esophagus were compared with findings in 570 younger patients with esophagectomy in the period 1982 to 1996. Changes in perioperative outcome and survival between 1982 to 1989 and 1990 to 1996 were separately analyzed. RESULTS: The resection rate in the elderly was 48% (167/345), lower than the 65% (570/874) resection rate in younger patients (p < 0.001). There were significantly more preoperative risk factors and postoperative medical complications in the elderly, but no significant differences were observed in surgical complications. The 30-day mortality rate was higher in the elderly (7.2%) than in younger patients (3.0%) (p = 0.02), but the hospital mortality rate was not significantly different in the elderly (18.0%) and younger age groups (14.4%) (p = 0.27). The long-term survival after curative resection in elderly patients was worse than younger patients (p = 0.01). However, when deaths from unrelated medical conditions were excluded from analysis, survival was similar between the two age groups (p = 0.23). A comparison of data for the periods 1982 to 1989 and 1990 to 1996 revealed that the resection rate had increased from 44% to 54% in the elderly, with significantly fewer postoperative complications and lower 30-day and hospital mortality rates. Long-term survival has also improved, although this has not reached a statistically significant level. CONCLUSIONS: With current surgical management, esophagectomy for carcinoma of the esophagus can be carried out with acceptable risk in the elderly, but intensive perioperative support is required. The improved results of esophagectomy in the elderly in recent years are attributed to increased experience and better perioperative management. Long-term survival was similar to that of younger patients, excluding deaths caused by unrelated medical conditions.     

Cyclin D1 amplification as a new predictive classification for squamous cell carcinoma of the esophagus, adding gene information

The cyclin D1, referred to as PRAD-1, has been mapped to the 11q13 region, and its expression has been detected in squamous cell lines and several primary esophageal carcinomas. We assessed cyclin D1 amplification in 122 squamous cell carcinomas of the esophagus. Samples for DNA extraction were obtained from formalin-fixed paraffin-embedded specimens, and 10 microgram of each DNA sample were subjected to slot blot analysis. The presence of more than three gene copies was considered evidence of gene amplification. Amplification of cyclin D1 was detected in 28 (23%) of 122 cases of squamous cell carcinoma of the esophagus. There were no significant differences between the clinicopathological background factors in groups positive and negative for cyclin D1 amplification, but the survival rate of patients exhibiting amplification was significantly lower (P < 0.001). The groups were stratified according to the pN (pathological N category) factor and pT (pathological T category) factor in the TNM classification, and the cumulative survival rates in the amplification groups were always significantly lower. Amplification of cyclin D1 was correlated with distant organ metastasis after curative operations, but there was no significant difference in lymph node recurrence rates of patients with or without amplification. Cyclin D1 amplification had the second highest partial regression coefficient in the multivariate analysis, after the pN factor. Amplification of cyclin D1 was independent of the TNM classification as a prognostic factor, and was a useful marker for predicting outcome and distant organ metastasis in patients with squamous cell carcinoma of the esophagus. It appears that appropriate treatment can be selected by evaluating both TNM factors and cyclin D1 amplification.     

Use of concurrent chemotherapy, accelerated fractionation radiation, and surgery for patients with esophageal carcinoma

BACKGROUND: The results of a Phase II study of concurrent chemotherapy and accelerated fractionation radiation therapy followed by surgical resection for patients with both adenocarcinoma and squamous cell carcinoma of the esophagus are presented. Pretreatment and postinduction staging were correlated with pathologic findings at surgery to assess the role of surgical resection and the predictive value of noninvasive staging techniques. METHODS: Patients received 2 induction courses with 4-day continuous intravenous infusions of cisplatin (20 mg/m2/day) and 5-fluorouracil (1000 mg/m2/day) beginning on Day 1 and Day 21, concurrent with a split course of accelerated fractionation radiation (1.5 grays [Gy] twice daily, to a total dose of 45 Gy). All patients were subsequently referred for surgical resection. A single, identical postoperative course of chemotherapy and 24 Gy accelerated fractionation radiation was planned for patients with residual tumor at surgery. RESULTS: Seventy-four patients were entered on this study; 72 patients were considered eligible and evaluable. Induction toxicity included nausea (85%), increased dysphagia (90%), neutropenia (<1000/mm3) (43%), thrombocytopenia (<20,000/mm3) (10%), and reversible nephrotoxicity (8%). Sixty-seven patients (93%) underwent surgery, and 65 (90%) were found to have resectable tumors. Twelve of these patients (18%) died perioperatively, and 18 (27%) had no residual pathologic evidence of disease. Resolution of symptoms and normalization of radiographic studies, endoscopy, or esophageal ultrasound did not identify pathologic complete responders accurately. No patient completing induction therapy and surgery experienced a locoregional recurrence. The Kaplan-Meier 4-year projected recurrence free and overall survival rates were 49% and 44%, respectively. CONCLUSIONS: Although this regimen is feasible, there was significant preoperative toxicity and perioperative mortality. Nonetheless, the recurrence free and overall survival rates were encouraging. However, no staging tool can predict a pathologic complete response after induction therapy accurately, suggesting a continued need for surgical resection.     

Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer

BACKGROUND: We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer. METHODS: Preoperative chemotherapy for patients randomly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil. Surgery was performed two to four weeks after the completion of the third cycle; patients also received two additional cycles of chemotherapy after the operation. Patients randomly assigned to the immediate-surgery group underwent the same surgical procedure. The main end point was overall survival. RESULTS: Of the 440 eligible patients with adequate data , 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery. After a median possible study time of 55.4 months, there were no significant differences between the two groups in median survival: 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who underwent immediate surgery (P=0.53). At one year, the survival rate was 59 percent for those who received chemotherapy and 60 percent for those who had surgery alone; at two years, survival was 35 percent and 37 percent, respectively. The toxic effects of chemotherapy were tolerable, and the addition of chemotherapy did not appear to increase the morbidity or mortality associated with surgery. There were no differences in survival between patients with squamous-cell carcinoma and those with adenocarcinoma. Weight loss was a significant predictor of poor outcome (P=0.03). With the addition of chemotherapy, there was no change in the rate of recurrence at locoregional or distant sites. CONCLUSIONS: Preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with epidermoid cancer or adenocarcinoma of the esophagus.     

Witzel gastrostomy in gynecologic surgery

From 1965 to 1990, 46 cases of malignant nasopharyngeal tumours were diagnosed in Iceland. The incidence rate is as low as in other Western countries, 0.6/100,000 per year. Histo-pathological diagnosis were as follows: Undifferentiated carcinoma 45%; squamous cell carcinoma 30%; non-keratinizing carcinoma 7%; and plasmacytoma 9%; lymphoma 7%; rhabdomyosarcoma 2%. Four per cent were diagnosed at stage I, 13% at stage II, 29% at stage III and 54% at stage IV. The overall crude survival at 10 years from diagnosis was 28.3%. The following factors were found to have a prognostic value: Stage of disease, size of tumour (T-classification) and age at diagnosis. Nodal stage (N-classification) alone and sex were not found to be prognostic factors. There was no difference in survival among the different WHO types of cancer. Patients with carcinoma were all treated with radiotherapy. The survival of those who received more than 60 Gy was better than of those who received 60 Gy or less (p = 0.04).     

Concurrent carboplatin/5FU and radiotherapy compared to radiotherapy alone in locally advanced cervical carcinoma: a case-control study

AIMS AND BACKGROUND: Despite the introduction of innovative techniques in radiotherapy (RT) delivery, no significant improvement in survival has been achieved in the last decades. Concurrent chemoradiation therapy (CRT) is one of the several avenues being explored to improve the results. METHODS AND STUDY DESIGN: Twenty-eight women with locally advanced squamous cell carcinoma of the uterine cervix were treated with CRT comprising a combination of external and intracavitary RT, along with 3 cycles of 5-fluorouracil (5-FU) and carboplatin. Toxicity, pelvic control rate and disease-free survival achieved in this group of patients were compared in a case-control study with those of a group of 28 patients with similar clinico-pathologic characteristics treated with radical RT alone at our institution. RESULTS: CRT was well tolerated, with 97% of the patients completing the protocol as planned. Acute toxicity, primarily hematologic, was significantly (P = 0.05) higher in the cases than in the controls (25% vs 3%). One treatment-related death occurred in a stage III patient in the CRT group. The median follow-up was 55 months (range, 20-156) in the RT group and 20 months (range, 14-46) in the CRT group. Pelvic control rate, disease-free survival and overall survival were not significantly different in the two groups. Estimated 5-year survival rate was 70% and 66% respectively for the RT and CRT group. CONCLUSIONS: Concomitant carboplatin/5-FU and radiotherapy is a safe and tolerable means of treatment for locally advanced cervical cancer. In our study, however, concurrent CRT did not result in a significant improvement in pelvic control rate or survival compared to standard conventional radiotherapy.     

Expression of the double-stranded RNA-dependent protein kinase (p68) in squamous cell carcinoma of the head and neck region

OBJECTIVE: p68 is an interferon-inducible protein kinase that is believed to be an important factor in the regulation of both viral and cellular protein synthesis. We have previously shown that p68 expression correlates with differentiation in a variety of tumors, including squamous cell carcinoma of the head and neck region. The current study aims to identify the prognostic significance of p68 expression in squamous cell carcinoma of the head and neck. DESIGN: Archival material from a cohort of 75 patients with primary squamous carcinomas of the head and neck was immunostained for p68 with the monoclonal antibody TJ4C4. Overall scores for p68 expression were tabulated based on staining intensity and percentage of immunoreactive tumor cells. Clinical information including tumor grade, stage, site, treatment, disease-free, and total survival was tabulated and compared by p68 expression group. SETTING: Veterans Administration Lakeside Medical Center and outpatient clinics (Northwestern University and Veterans Administration Lakeside Medical Center, Chicago, Ill). PATIENTS: Seventy-five consecutive patients with primary squamous cell carcinoma of the head and neck (excluding the esophagus), with tissue blocks available for study, a known primary site, no history of prior carcinoma, and demographic and follow-up information available. MAIN OUTCOME MEASURED: Disease-free and overall survival rates. RESULTS: While there was a wide range of outcomes within each group, as a group, high levels of p68 expression correlated with a lower incidence of recurrent or residual disease and longer disease-free and total survival times compared with groups with lower levels of p68 expression. These differences could not be explained on differences in patient age, tumor grade, and TNM stage. CONCLUSIONS: High-level p68 expression is associated with prolonged disease-free and overall survival in a series of patients with squamous cell carcinoma of the head and neck region. Additional study is needed to monitor changes in p68 expression with treatment or tumor progression.     

Induction cisplatin/vinblastine and irradiation vs. irradiation in unresectable squamous cell lung cancer: failure patterns by cell type in RTOG 88-08/ECOG 4588. Radiation Therapy Oncology Group. Eastern Cooperative Oncology Group

PURPOSE: To analyze disease failure patterns by pretreatment characteristics and treatment groups in a prospective randomized trial. METHODS AND MATERIALS: Patients with medically inoperable Stage II, unresectable IIIA and IIIB nonsmall cell lung cancer with KPS > or =70 and weight loss < or =5% were randomized to one of three treatment groups: standard radiation therapy with 60 Gy at 2.0 Gy per day (STD RT), induction chemotherapy with cisplatin 100 mg/m2 days 1 and 29 with vinblastine 5 mg/m2 weekly for 5 weeks followed by 60 Gy at 2.0 Gy per day (CT + RT), or hyperfractionated radiation therapy with 69.6 Gy at 1.2 Gy b.i.d. (HFX RT). Of 490 patients enrolled, 458 were evaluable. Minimum and median periods of observation for this analysis were 4 years and 6 years, respectively. RESULTS: Pretreatment characteristics were equally distributed. Toxicities were previously reported. Median survival rates were 11.4, 13.6, and 12.3 months for STD RT, CT + RT, and HFX RT, respectively (log rank p = 0.05, Wilcoxon p = 0.04). Survivals were 20, 31, and 24% at 2 years, and 4, 11, and 9% at 4 years in the STD RT, CT + RT, and HFX RT groups, respectively. There were no differences in local tumor control rates among the treatments. Patterns of first failure showed less distant metastasis (DM) (other than brain) for CT + RT compared to the RT alone arms (p = 0.04). Within squamous cell carcinoma (SCC), DM (other than brain) rates were 43%, 16%, and 38% in SCC for STD RT, CT + RT, and HFX RT, respectively (p = 0.0015). Patients with peripheral/chest wall lesions were significantly more likely to fail first in the thorax when treated on STD RT compared to CT + RT and HFX RT (p = 0.009). Survival rates were similar among the treatment arms for patients with squamous cell carcinoma. Among patients with nonsquamous cell carcinoma, failure patterns did not differ by treatment group, but survival was significantly better in those who were treated by induction chemotherapy (p = 0.04). CONCLUSION: Patients with squamous cell carcinoma treated on the CT + RT arm had a significant reduction of first DM other than brain, but there was difference in survival. Survival favored CT + RT in nonsquamous carcinoma despite similar failure patterns. Reasons for improved survival with CT + RT in NSCLC are not yet available.     

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PURPOSE: To compare the response rates, toxicities and survival durations of elderly patients (70 years of age or more) with those of younger patients (less than 70 years of age) with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. PATIENTS AND METHODS: We analyzed retrospectively the data of 203 assessable patients entered on a prospective randomized trial of cisplatin-based combination chemotherapy. Chemotherapy consisted of three dosage regimens: (1) vindesine and cisplatin (VP); (2) mitomycin, vindesine and cisplatin (MVP); or (3) etoposide and cisplatin alternating with vindesine and mitomycin (EP/VM). RESULTS: A greater proportion of elderly patients had localized disease and more squamous cell carcinoma than non-elderly patients. The overall response rates were 44% in the elderly group and 28% in the non-elderly group. In the EP/VM arm, the response rate was significantly better in the elderly group than in the non-elderly group. The frequency of grade 4 leukocytopenia in the MVP and EP/VM arms in the elderly group was significantly greater than in the non-elderly group (P < 0.05). No differences were found in nonhematological toxicities between the two groups. There was no difference in overall survival between the groups. CONCLUSION: Elderly patients treated with mitomycin-containing regimens have higher hematologic toxicities than younger patients. The results of this study are consistent with the previously reported pharmacologic data on mitomycin suggesting altered pharmacokinetics in elderly patients. The improved response rate in the elderly patients was probably because more elderly patients had earlier disease, squamous cell carcinoma and better performance status. Cisplatin-based chemotherapy was tolerable for most elderly NSCLC patients with good performance status.     

Cervical cancer survival in a high risk urban population

BACKGROUND: Cervical cancer remains an important public health problem, particularly for the urban minority population. To the authors' knowledge, determinants of cervical cancer survival have not been studied in this high risk population. METHODS: This study included all 158 women diagnosed and treated for invasive cervical cancer from January 1, 1986, through December 31, 1992, at the Grady Memorial Hospital and Clinics (Atlanta, GA). Medical records were abstracted to determine age at diagnosis, race, International Federation of Gynecology and Obstetrics (FIGO) clinical stage, treatment, and survival. Pathologic material was reviewed to confirm the diagnosis. RESULTS: Most patients (80%) were African American, and the stage distribution was similar for African American and white patients. Sixty-six (42%) had FIGO Stage I disease; 50%, Stage II or III; and 8%, Stage IV. Four-year actuarial survival differed significantly according to clinical stage (Ia = 94%, Ib = 79%, II = 39%, III = 26%, IV = 0%). Overall survival was lower for patients with glandular carcinomas than for those with squamous cell carcinomas (26% vs. 55%, P = 0.09). This difference was almost entirely due to increased mortality in patients with Stage Ib adenocarcinomas (53% vs. 88% for squamous cell carcinoma, Stage Ib, P = 0.03). CONCLUSIONS: The major prognostic markers for cervical cancer survival in this high risk patient population were clinical stage and histology, factors identical to those identified for other populations.     

Basaloid squamous cell carcinoma of the esophagus: diagnosis and prognosis

BACKGROUND: Basaloid squamous cell carcinoma (BSCC) is a recently recognized, poorly differentiated variant of squamous cell carcinoma (SCC), which is located predominantly in the upper aerodigestive tract. METHODS: In this study, clinical and pathologic parameters of 17 BSCCs and 133 typical SCCs of the esophagus that underwent potentially curative resection (no distant metastases, no residual tumor) were compared. In addition, light microscopic, electron microscopic, and immunohistochemical features of BSCC were investigated, to determine whether this type of carcinoma could be differentiated from other poorly differentiated carcinomas of the esophagus. RESULTS: Light microscopic study showed that BSCC was composed of relatively small tumor cells, arranged in solid lobules with abundant comedo-type necrosis. BSCC was almost invariably accompanied by areas of concomitant typical SCC, foci of squamous cell differentiation, and/or severe squamous cell dysplasia or carcinoma in situ of the adjacent mucosa. Ultrastructurally, BSCC inconsistently showed features of squamous cell differentiation. Immunohistochemically, BSCC displayed poor reactivity for antibodies against wide-range cytokeratins and cytokeratin subtypes that are typical of squamous cell epithelia (cytokeratin 13 and cytokeratin 14). Infrequently, expression of Leu7, smooth muscle actin, and S-100 protein was found. In comparison with typical SCC, the characteristic features of BSCC were older patient age, higher proliferative activity (MIB-1 labelling index), and higher apoptotic indices. No differences were found with regard to pT classification, pN classification, tumor size, blood vessel invasion, lymphatic vessel invasion, neural invasion, or patient gender. Moreover, no differences in overall survival rates were found. CONCLUSIONS: BSCC is a distinct histopathologic variant of SCC, characterized by a poor degree of differentiation and high proliferative activity. However, after potentially curative resection, the prognosis of patients with BSCC of the esophagus does not differ from that of patients with typical SCC.     

Blockade of mitogen-activated protein kinase cascade signaling in interleukin 6-independent multiple myeloma cells

OBJECTIVE: There have been few studies concerning the clinical pathology of squamous cell carcinoma arising from ovarian mature cystic teratoma. Thus, the objective of this study is to determine clinicopathologic factors affecting survival in this rare tumor. METHODS: From September 1979 to June 1996, 37 patients with squamous cell carcinoma arising from ovarian mature cystic teratoma were treated by the Tokai Ovarian Tumor Study Group. A retrospective clinicopathologic and survival analysis of these patients was performed. The mode of infiltration was classified into expansive, moderately diffused, and diffused patterns. RESULTS: Although the 5-year survival rate was 94.7% and 80.0% for stage I and II patients, respectively, 12 of 13 patients with stage III died within 20 months (P = .0001). A significant difference was also observed between the survival of the groups with and without residual tumor at surgery (P = .0001). Pathologic features, grade, mode of infiltration, and vascular involvement were significant factors by univariate analysis. Multivariate analysis showed significant differences in survival related to grade (P = .0154) and mode of infiltration (P = .0053). The preoperative squamous cell carcinoma antigen level was significantly higher in the patients with squamous cell carcinoma arising from mature cystic teratoma than in patients with mature cystic teratoma (P < .0001). CONCLUSION: This study suggests that pathologic factors, grade, and mode of infiltration can provide valuable information for predicting the survival of patients with squamous cell carcinoma arising from mature cystic teratoma. In addition, squamous cell carcinoma antigen may be a useful marker to detect this disease preoperatively.     

5-Fluorouracil and cisplatin as palliative treatment of advanced oesophageal squamous cell carcinoma. A multicentre randomised controlled trial. The French Associations for Surgical Research

OBJECTIVE: To compare chemotherapy with no chemotherapy as palliative treatment for oesophageal squamous cell carcinoma. DESIGN: Randomised study. SETTING: Multicentre trial in France. SUBJECTS: Of 161 patients with histologically confirmed oesophageal squamous cell carcinoma located more than 5 cm from the mouth of the oesophagus, five were withdrawn because of protocol violation. The remaining 156 patients, 149 men and 7 women, mean (SD) age 58 (9) years range 36 to 77, were randomly allocated to either a control group without chemotherapy (n = 84) or a group treated by chemotherapy (n = 72). Patients were divided into four strata: I = complete resection of the tumour but with lymph node involvement (n = 62); II = incomplete resection of tumour leaving gross tumour behind (n = 58); III = no resection because of local or regional invasion (n = 22) ; and IV = no resection because of distant metastasis (n = 14). Exclusion criteria were histologically confirmed tracheobronchial involvement, oesophagotracheal fistula, Karnosky score < 50, cerebral metastases, or hepatic metastases occupying more than 30% of the liver, peritoneal carcinomatosis, associated or previously treated ear-nose-throat carcinoma, or complete resection of tumour without lymph node involvement. INTERVENTIONS: 5 fluorouracil (5FU) and cisplatin (CDDP) were given in 5-day courses, once every 28 days, for a maximum of eight cycles. 5 FU, 1 g/m2, was infused for 24 hours after a water overload, during five days. Cisplatin was given either in one dose of 100 mg/m2 at the beginning of the cycle or 20 mg/m2/day over three hours for five days. Duration of treatment ranged from 6-8 months. OUTCOME MEASURES: Median and actuarial survival. The subsidiary endpoint was quality of survival judged by complications of treatment, swallowing disorders, and the duration of ability to feed normally. RESULTS: There was no difference in survival, either overall (median = 12 months) or in any of the strata. There were however significantly more patients with neurological (p < 0.003), haematological (p < 0.0001), and renal (p < 0.0002) complications in the treated group compared with the control group. Four patients (6%) died of complications of chemotherapy. The course of swallowing disorders did not differ between the two groups. The duration of autonomous oral feeding was exactly the same in both groups (median = 10.5 months). CONCLUSION: The results suggest that 5FU and CDDP do not help in patients with squamous cell carcinoma of the oesophagus whether or not the tumour has been resected.     

Expression of p21WAF1 predicts outcome of esophageal cancer patients treated by surgery alone or by combined therapy modalities

The p21WAF1 protein is an important regulator of the cell cycle. Its expression and prognostic significance were investigated immunohistochemically in samples of normal esophageal squamous epithelium (n = 10), severe squamous cell dysplasia (n = 20), carcinoma in situ (n = 14), permanent esophageal squamous cell carcinoma cell lines (n = 3), and invasive squamous cell carcinomas treated either by potentially curative resection (n = 172) or by combined modality therapy (radiochemotherapy +/- surgery; n = 38). Whereas p21WAF1 expression in the normal epithelium was restricted to a few cells adjacent to the basal cell layer, p21WAF1 overexpression was frequently found in preneoplasias and invasive carcinomas. Expression of p21WAF1 in invasive carcinomas was not correlated with tumor differentiation, pT category, or pN category. Among carcinomas treated by potential curative resection, univariate (P = 0.0025) and multivariate (P = 0.0081) survival analysis showed significant correlation of strong p21WAF1 expression (> or =50% p21WAF1-positive tumor cells) with poor overall survival. Univariate survival analysis (P = 0.0006) revealed the same prognostic influence in the group of patients treated by combined modality therapy. We conclude that overexpression of p21WAF1 protein is a frequent event in preneoplasias and neoplasias of the esophagus. Immunohistochemical examination of p21WAF1 expression may provide important prognostic information for decision-making in the treatment of patients with esophageal cancer.     

Carcinoma of the nasopharynx in young patients

PURPOSE: To provide an analysis of eighteen cases of adolescent nasopharyngeal carcinoma treated between 1971 and 1989. METHODS AND MATERIALS: Between 1971 and 1989, 48 cases of nasopharyngeal carcinoma were evaluated at the Medical College of Georgia Hospital and Clinics. Eighteen patients between the ages of 9 and 29 years were treated at the Georgia Radiation Therapy Center. All patients presented for treatment with (AJCC) Stage IV disease. Fifteen patients with lymphoepithelioma and three with squamous cell carcinoma histologies received definitive radiation therapy to a median dose of 64.8 Gy. Males outnumbered females by more than 2:1 and the majority of patients (67%) were black. Nine patients received multiagent adjuvant chemotherapy. RESULTS: Thirteen patients are alive from 7 to 166 months (median 32 months) including three with disease at 17, 24, and 132 months. Overall and disease-free survival at 5 and 10 years were 63% and 54%, respectively. Five patients died from disease; four patients had pulmonary metastases while one had CNS metastasis. Eighty percent of relapses occurred within the first 2 years following treatment. Acute and chronic toxicities were limited, consisting primarily of mucositis and xerostomia. Radiation doses of 65 Gy or more (p = 0.049) and age greater than 20 years (p = 0.005) were positive prognosticators for survival. Adjuvant chemotherapy, race, and sex were not found to be of prognostic value. Disparities in the distribution of patients with lymphoepithelioma and squamous cell histologies and the presentation of advanced regional disease precluded analysis for prognostic significance of histology and nodal status in this series. CONCLUSION: The results of the present series compare favorably with those published from other institutions. High doses of radiation and a high systemic failure rate continue to be the fundamental obstacles to effective management and enhanced survival for patients with nasopharyngeal carcinoma.     

Use of echocardiography in the management of congestive heart failure in the community

BACKGROUND: Inhibition of apoptosis, or programmed cell death, may be critical both in the development of cancer and in determining response to therapy. The authors examined the expression of two related apoptotic inhibitors, Bcl-2 and Bcl-xL, in pretreatment biopsies from a series of 42 patients with squamous cell carcinoma of the head and neck. The observed pattern of apoptotic inhibitor expression was compared with that of the p53 gene product, another factor implicated in carcinogenesis and therapeutic responsiveness. METHODS: Formalin fixed, paraffin embedded tumor biopsies from 42 patients with locally advanced squamous cell carcinoma of the head and neck were analyzed by immunohistochemistry using antibodies specific for Bcl-xL, Bcl-2, and p53. Measures of clinical outcome, including disease specific survival and overall survival, were compared among the groups. RESULTS: The majority of the tumors demonstrated enhanced expression of either Bcl-2 or Bcl-xL compared with surrounding normal epithelium. Fifty-two percent of the tumors had up-regulated Bcl-xL, and 17% had up-regulated Bcl-2. There was no overlap between these groups. Expression of Bcl-2, but not Bcl-xL, was correlated with improved disease specific survival. Immunohistochemically detectable p53 expression (48% of tumors) was not found to correlate with expression of either Bcl-xL or Bcl-2 and, in this series, was not a predictor of clinical outcome. CONCLUSIONS: These results suggest that disruption of apoptotic control pathways is an important event in the evolution of squamous cell carcinoma of the head and neck. A common mechanism for this disruption involves overexpression of Bcl-xL, Patients whose tumors demonstrate Bcl-2 positivity, even with locoregionally advanced disease, appear to have a high likelihood of cure with aggressive combined modality therapy and may be treated successfully with less toxic therapy.     

Base of tongue carcinoma: patterns of failure and predictors of recurrence after surgery alone

Between January 1971 and December 1986, 55 patients with squamous cell carcinoma of the tongue base underwent complete surgical resection with curative intent. No preoperative or postoperative adjuvant therapy was administered. The study group consisted of 41 men and 14 women (median age 61 years). All patients were followed until death (39 patients) or for a median of 9.4 years. Local control at 5 years was 74%. No predictors of local recurrence were discovered. Control in the dissected neck at 5 years was 68%. Control of cancer above the clavicles at 5 years was 48%. Distant metastases developed in 14% of the patients by 5 years. Cause-specific survival at 5 years was 65%. A Cox multivariate regression analysis revealed that pathologic N stage was the only significant independent predictor of recurrence in the dissected neck, recurrence above the clavicles, and cause-specific survival. The 5-year overall survival was 55%. Surgical mortality was 4%.