Advances in the treatment of esophageal carcinoma

Recent changes in the epidemiology of esophageal carcinoma now recognize adenocarcinoma as the predominant histologic cell type. Barrett's esophagus and dysplasia in this epithelium identify patients who are at risk of developing invasive adenocarcinoma. This neoplasm is not a single entity with a consistently poor prognosis, and disease stage is important for determining therapy. These findings offer the potential for further development of therapeutic regimens. Endoscopic esophageal ultrasound is an accurate and reproducible staging tool. It allows the physician to determine clinical stage and modify treatment. T2 N0 M0 or lesser stage tumors have acceptable surgical cure rates, and patients should undergo immediate resection. Patients with more advanced T3 or N1 tumors have a potential for cure but do poorly with surgery alone. These patients should be considered for multimodality therapy. Palliative therapy should be given to patients with hematogenous metastatic disease. Treatment stratification by stage proves that esophageal carcinoma is not a uniformly fatal disease without hope for cure.     

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.     

Barrett's esophagus: pathogenesis, epidemiology, functional abnormalities, malignant degeneration, and surgical management

Barrett's esophagus (i.e. columnar epithelial metaplasia in the distal esophagus) is an acquired condition that in most patients results from chronic gastroesophageal reflux. It is a disorder of the white male in the Western world with a prevalence of about 1/400 population. Due to the decreased sensitivity of the columnar epithelium to symptoms, Barrett's esophagus remains undiagnosed in the majority of patients. Gastroesophageal reflux disease in patients with Barrett's esophagus has a more severe character and is more frequently associated with complications as compared with reflux patients without columnar mucosa. This appears to be due to a combination of a mechanically defective lower esophageal sphincter, inefficient esophageal clearance function, and gastric acid hypersecretion. Excessive reflux of alkaline duodenal contents may be responsible for the development of complications (i.e., stricture, ulcer, and dysplasia). Therapy of benign Barrett's esophagus is directed towards treatment of the underlying reflux disease. Barrett's esophagus is associated with a 30- to 125-fold increased risk for adenocarcinoma of the esophagus. The reasons for the dramatic rise in the incidence of esophageal adenocarcinoma, which occurred during the past years, are unknown. High grade dysplasia in a patient with columnar mucosa is an ominous sign for malignant degeneration. Whether an esophagectomy should be performed in patients with high grade dysplasia remains controversial. Complete resection of the tumor and its lymphatic drainage is the procedure of choice in all patients with a resectable carcinoma who are fit for surgery. In patients with tumors located in the distal esophagus, this can be achieved by a transhiatal en-bloc esophagectomy and proximal gastrectomy. Early adenocarcinoma can be cured by this approach. The value of multimodality therapy in patients with advanced tumors needs to be shown in randomized prospective trials.     

A randomized study of chemotherapy, radiation therapy, and surgery versus surgery for localized squamous cell carcinoma of the esophagus

BACKGROUND: Despite well-established surgical approaches, the prognosis for patients with squamous cell carcinoma of the esophagus remains dismal. To assess the benefit of adjuvant chemotherapy and radiation therapy (CRT), a randomized trial with and without sequential preoperative CRT was undertaken; CRT combined 20 Gy and two courses of 5-FU and cisplatin. METHODS: Patients were included on the basis of the following criteria: squamous cell carcinoma of the esophagus, younger than 70 years of age, World Health Organization status below 2, estimated survival time greater than 3 months, and no previous treatment for the cancer. Patients were not included if they had experienced a loss in body weight greater than 15% or had tracheoesophageal fistula, metastases, or uncontrollable infection. RESULTS: Eighty-six patients thus fulfilled the criteria for inclusion (41 CRT, 45 non-CRT). The groups were well-matched for age, sex, tumor location, size, and grade. Operative mortality was 8.5% and 7%, respectively, for each group with a 27-day hospital stay for both groups. Long-term survival was not significantly different, with 47% of both groups alive at 1 year. CONCLUSIONS: The authors concluded that this neoadjuvant treatment did not change operative mortality or survival time for patients with squamous cell carcinoma of the esophagus.     

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.     

Hypothyroidism after x irradiation to the neck: three case reports and a brief review of the literature

Three patients who developed hypothyroidism after x irradiation to the neck are presented. The first two cases demonstrate that patients can develop clinical and chemical hypothyroidism after a very short interval following radiotherapy. Hypothyroidism developed in the first patient in the absence of surgical manipulation of the neck, or a large iodine load 4 months after receiving 6800 rad of x-ray therapy to his neck for carcinoma of the larynx. The second patient developed hypothyroidism approximately 6 months after his radiotherapy for carcinoma of the esophagus. Both of these patients demonstrated high titers of serum antithyroid antibodies. A third patient with Hodgkin's disease did not manifest clinical symptoms and signs of hypothyroidism until 6 years after radiation therapy. These cases demonstrate the variability of onset of hypothyroidism after radiotherapy and emphasize the need for careful evaluation of thyroid function before and after neck irradiation.     

Esophagogastric fistula: a complication of Crohn's disease--case report and review of the literature

Esophagogastric fistula formation as a complication of esophageal Crohn's has been reported in only one case in the literature. In addition, only eight cases of esophageal fistulae of any type have been reported in the setting of Crohn's disease. Unlike the more often described superficial, aphthous disease of the esophagus, response of fistulae to medical therapy has been disappointing, and recurrence and progression are likely. Surgery remains the primary modality for refractory disease. The roles of salicylates, antibiotics, immunosuppressive agents, sealants, and intralesional steroid injections have not been well defined. We present a case of severe, refractory Crohn's disease with fistula formation between the esophagus and stomach, and concomitant involvement of the oropharynx, duodenum, terminal ileum, and cecum.     

The treatment of excessive somnolence with stimulant drugs

In this paper we report on the long-term results achieved in 75 patients with superficial carcinoma of the thoracic esophagus who have been treated since 1965 with esophagectomy at our institute. In three of these patients, the carcinoma was limited to the epithelium (intra-epithelial carcinoma), while in 13 cases it was confined to the mucosa, and in 59 cases to the submucosa. There was no lymph node metastasis in patients with intra-epithelial or mucosal carcinoma, but lymph node involvement was found in 13 (22.0%) of the 59 cases of submucosal carcinoma. The five-year survival rate of patients with intra-epithelial carcinoma and mucosal carcinoma was 100%, which was significantly better than that for carcinoma invading the submucosa (49%). The five-year survival rate for patients with lymph node involvement was only 46%, which was significantly worse than that for patients without lymph node involvement (60%). No recurrence occurred in patients with intra-epithelial carcinoma or mucosal carcinoma, while recurrent disease occurred in 19 (32.2%) of the 59 patients with submucosal carcinoma. Lymph node recurrence and hematogenic recurrence such as lung and bone metastasis were the most frequent developments in patients with submucosal carcinoma of the esophagus.     

Design and synthesis of small semi-mimetic peptides with immunomodulatory activity based on myelin basic protein (MBP)

Bile reflux has been implicated in the pathogenesis and malignant degeneration of Barrett's esophagus, but clinical studies in patients with adenocarcinoma arising in Barrett's esophagus are lacking. Ambulatory esophageal measurement of acid and bile reflux was performed with the previously validated fiberoptic bilirubin monitoring system (Bilitec) combined with a pH probe in 20 asymptomatic volunteers, 19 patients with gastroesophageal reflux disease (GERD) but no mucosal injury, 45 patients with GERD and erosive esophagitis, 33 patients with GERD and Barrett's esophagus, and 14 patients with early adenocarcinoma arising in Barrett's esophagus. Repeat studies were done in 15 patients under medical acid suppression and 16 patients after laparoscopic Nissen fundoplication. The mean esophageal bile exposure time showed an exponential increase from GERD patients without esophagitis to those with erosive esophagitis and benign Barrett's esophagus and was highest in patients with early carcinoma in Barrett's esophagus (P <0.01). Pathologic esophageal bile exposure was documented in 18 (54.5%) of 33 patients with benign Barrett's esophagus and 11 (78.6%) of 14 patients with early adenocarcinoma in Barrett's esophagus. Nissen fundoplication but not medical acid suppression resulted in complete suppression of bile reflux. Bile reflux into the esophagus is particularly prevalent in patients with Barrett's esophagus and early cancer. Bile reflux into the esophagus can be completely suppressed by Nissen fundoplication but not medical acid suppression alone.     

The change in laser usage in gastroenterology--the status in 1997

Since the establishing of laser technology in gastroenterology there has been a change in the indications for laser therapy and numerous new laser systems have been introduced in basic and clinical research. First the argon laser and later on the Nd:YAG laser were used mainly for bleeding peptic lesions, today emphasis is on palliative desobliteration of advanced esophageal and rectosigmoidal carcinoma. Moreover, in selected cases it is used for curative ablation of early carcinoma and dysplasia. A new field of application is photocoagulation of the "watermelon stomach". Despite of promising ablation results the erbium:YAG and holmium:YAG laser became not yet established in gastroenterology. Also the KTP laser is rarely used e.g. for treatment of telangiectasia. Difficult bile duct stones can be highly effective fragmented intracorporally by means of laser lithotripsy; an automatic stone-tissue discrimination system avoids uncontrolled injury of the bile ducts. The hitherto experimental interstitial laser therapy of primary and secondary liver malignancies shows excellent results, but online monitoring of the expansion of the necrosis is still a problem. Thermal probes, MRT technology and duplex sonography are under current evaluation. Photodynamic therapy (PDT) is now, after numerous pilot studies, investigated with larger numbers of patients. First results show a marked effectiveness in ablation of dysplasia and mucosal carcinoma. The photosensitizer 5-aminolaevulinic acid seems to be particularly effective for ablation of Barrett's mucosa and m-THPC for treatment of local carcinoma. Palliative PDT of bile duct cancer may help to avoid repeated endoprosthetic treatment. The possibilities and limitations of light induced fluorescence diagnostics of severe dysplasia and carcinoma in situ is now being evaluated intensively. This method might in future facilitate the endoscopic diagnosis of dysplasia in Barrett's esophagus and chronic inflammatory bowel disease.     

A randomized comparison of dilatation alone versus dilatation plus laser in patients receiving chemotherapy and external beam radiation for esophageal carcinoma

Most patients with carcinoma of the esophagus have advanced disease at presentation. Since cure is usually not possible, the goal of treatment is the palliation of dysphagia. Palliative modalities include bougies, balloons, stents, tumor probe, laser, surgery, chemotherapy, and radiation. In recent years, combined chemotherapy and radiation has shown promising results. However, the relief of dysphagia is slow and frequently incomplete. We compared the effectiveness of dilatation alone versus dilatation plus Nd-YAG laser therapy for the relief of dysphagia while assessing the role of chemotherapy and radiation as an adjunct to surgery. Fifteen patients with squamous cell carcinoma of esophagus who were deemed fit for intensive chemotherapy and radiation were randomized to receive either dilatation alone (N = 7) or dilatation plus laser (N = 8); the end-point for initial success was the passage of a 45 French Savary dilator, and the relief of dysphagia. At entry, 13 of these 15 patients were judged potentially resectable. However, after chemotherapy and radiation, only 3 of 13 (20%) patients could be offered surgery; the remainder were considered too poor a surgical risk. Follow-up was for 30 months, or until death. Further dilatations were performed as needed for relief of dysphagia. No difference was observed between the laser plus dilatation and the dilatation alone group with respect to the degree of dysphagia, weight record, quality of life index (Karnofsky score), or mortality rate. Our results indicate that in patients undergoing chemotherapy and radiation for esophageal carcinoma, dilatation alone provides adequate palliation of dysphagia, and in these patients, chemotherapy and radiation is a poor adjunct to surgical treatment.     

Squamous carcinoma of the esophagus with extensive pagetoid dissemination

A case of squamous carcinoma of the esophagus with pagetoid spreading in a 59-year-old male in presented. Signs of glandular differentiation (PAS-diastase, Alcian blue) and CEA were negative in the Paget-like cells. Pagetoid spreading of squamous carcinoma and true Paget's disease are very similar histologically and very rare in the esophagus (only 6 cases reported) and they must be differentiated from each other. Paget's disease demonstrates glandular differentiation and the cells are CEA positive. The absence of glandular differentiation in the Paget-like cells of pagetoid spreading versus Paget's disease may be a good criteria to differentiate these diseases.     

Effects of intra-amygdala R(+) 7-OH-DPAT on intra-accumbens d-amphetamine-associated learning. II. Instrumental conditioning

BACKGROUND: Recurrence of rectal and colonic carcinoma remains substantial despite apparently curative surgery. Adjuvant therapy has been applied to improve prognosis. METHODS: This review evaluates the use of adjuvant therapy in the management of resectable rectal and colonic carcinoma. It assesses critically the evidence supporting the addition of radiotherapy, chemotherapy, chemoradiotherapy and other treatment modalities to optimal surgery. RESULTS: In the case of rectal tumours, preoperative is more effective than postoperative radiotherapy; It can significantly reduce the incidence of local tumour recurrence. A number of trials have tended towards showing a survival advantage and a recent large randomized trial has shown a significant improvement in survival in patients with Dukes C tumours. Postoperative chemoradiotherapy is associated with a survival benefit and is standard therapy in the USA, although it is associated with increased toxicity. The effectiveness of preoperative chemoradiotherapy is currently being investigated. Postoperative fluorouracil-containing chemotherapy has resulted in a survival advantage in patients with Dukes C colonic tumours; such therapy may be administered either systemically or intraportally. The evidence of benefit with rectal tumours is more limited. Immunotherapy has been studied to a limited extent and the use of a tumour-directed monoclonal antibody has produced a survival advantage in a single trial. CONCLUSION: Preoperative radiotherapy and postoperative chemoradiotherapy can produce a survival advantage in patients with Dukes C rectal carcinoma and reduce local recurrence. Postoperative fluorouracil-containing chemotherapy can produce a survival advantage in those with Dukes C colonic cancer. The optimal use and combination of adjuvant therapy remains uncertain.     

Postmenopausal oestrogens and arteries

Postmenopausal oestrogen use is associated with a significant reduction in cardiovascular morbidity and mortality. The fact that a large scale controlled trial has not been conducted is a valid criticism, but the epidemiological data are compelling and there is evidence of biologically plausible mechanisms which may mediate this effect. Postmenopausal HRT also abolishes climacteric symptoms and conserves bone. For the postmenopausal woman who has had a hysterectomy, unless there are compelling reasons to the contrary, we believe that unopposed oestrogen therapy should be offered routinely. Women who still have a uterus (and these form the majority of potential HRT users) require oestrogens with cyclical progestogens. Whether such opposed therapy results in any reduction in cardiovascular protection needs to be addressed urgently. Meanwhile, it could be argued that these women should also be offered HRT routinely. Indeed, a recent consensus conference (Lobo & Speroff 1994) concluded that because of the magnitude of cardiovascular disease as a cause of morbidity and mortality, the beneficial role of estrogen in the primary prevention of cardiovascular disease in most women outweighs its potential risk. At the present time, there are insufficient data to indicate whether there are any groups of women for whom the risks may be too great to prescribe some form of estrogen therapy. As life expectancy increases in developed countries, such reductions in the leading cause of mortality are likely to benefit not only the individual woman, but the society in which she lives.     

Early results of a prospective study of hormone therapy for patients with locally advanced prostate carcinoma

BACKGROUND: Locally advanced prostate carcinoma is usually not curable with surgery or radiation therapy. Primary hormone therapy is an alternative therapeutic option, but contemporary prospective studies of the outcomes of such therapy are not available. METHODS: The authors conducted a prospective, hospital-based study of gonadal androgen ablation with deferred antiandrogen therapy in 103 men with prostate carcinoma clinically classified as T3-4NXM0. The median potential follow-up was 51 months (range, 36-74 months), and the median period of observation was 43 months (range, 6-74 months). RESULTS: Each patient experienced regression of the primary tumor, and none experienced significant morbidity from the primary tumor during the study period. The projected 5-year cause specific, metastasis free, PSA disease free (no PSA elevation > 1.0 ng/mL after the beginning of antiandrogen therapy), and all-cause survival rates were 84%, 84%, 68%, and 58%, respectively. CONCLUSIONS: Primary hormone therapy is a reasonable treatment option for locally advanced prostate carcinoma in elderly men or in men with significant comorbid disease who request therapeutic intervention.     

Genitourinary small cell carcinoma: determination of clinical and therapeutic factors associated with survival

PURPOSE: We assessed the prognostic impact of genitourinary small cell carcinoma tumor and patient characteristics, and therapy. MATERIALS AND METHODS: We retrospectively reviewed the records of 180 patients with genitourinary small cell carcinoma in which patient and tumor characteristics, therapy, followup duration and survival status had been documented. Patient age, sex, primary site, histological features, tumor size, stage, locoregional therapy, systemic chemotherapy and hormonal manipulations were analyzed for association with survival. RESULTS: There were 106 cases of bladder, 60 prostatic, 8 renal and 6 ureteral small cell carcinoma. Median survival was 10.5 months overall, and 7 and 13 months for prostatic and bladder small cell carcinoma, respectively (p <0.0001 log rank analysis). In all cases metastatic disease at presentation (p <0.008, risk ratio 1.9) predicted poor survival on multivariate analysis. Radical surgery (p <0.0001, risk ratio 0.34) and cisplatin chemotherapy (p <0.0001, risk ratio 0.20) were the only factors that predicted improved survival on multivariate analysis. For prostatic small cell carcinoma primary surgical therapy (p <0.012, risk ratio 0.46) was the only parameter that predicted survival on univariate analysis. For bladder small cell carcinoma only cisplatin chemotherapy (p <0.0001, risk ratio 0.15) predicted survival on multivariate analysis. CONCLUSIONS: Genitourinary small cell carcinoma has a poor prognosis, which is worse in prostatic than bladder disease. Patient and tumor characteristics were not determinants of survival when prostatic and bladder small cell carcinoma were analyzed individually. For prostatic disease only primary surgical therapy was associated with prolonged survival, while for bladder disease cisplatin chemotherapy was associated with a favorable prognosis. We recommend considering primary surgical therapy for prostatic and cisplatin based chemotherapy for bladder small cell carcinoma.     

Significance of routine annual esophagram for early detection of carcinoma of the esophagus

BACKGROUND/AIMS: In order to achieve increased survival rates for patients with carcinoma of the esophagus, early detection of the disease is vital. Serial esophagrams were evaluated to clarify which interval would be effective for early detection of carcinoma of the esophagus during routine examination. MATERIALS AND METHODS: One hundred eighty-nine patients with carcinoma of the esophagus were grouped into three, according to the experience and the time of the previous roentgenograms before the definite diagnosis. RESULTS: Five patients were in Group 1, in which roentgenographic examination had been done within 12 months prior to the diagnosis. Retrospective observation revealed a slight but certain abnormal shadow at the same location as the esophageal tumor seen on the second films. In Group 2, seven had received an esophagram between 12 and 24 months before the diagnosis. In contrast to Group 1, neither abnormality nor findings indicating esophageal tumors were detected on the former x-ray films, in all seven cases. Group 2 was characterized by relatively small tumors and low stage of the disease. Mean tumor length was 4.1 +/- 2.9 cm, and three of seven were classified as Stage I and two as Stage IIA. On the other hand, most of the 177 patients in Group 3, with no previous examination of the esophagus within 24 months before the diagnosis, had far advanced disease. Mean tumor length was 6.3 +/- 2.6 cm. Only nine (5.1%) were classified as Stage I, whereas 115 (65.0%) were classified as Stage III or IV. CONCLUSION: In light of these data, for populations in which esophageal cancer frequently occurs, esophageal examination every 12 months will no doubt contribute towards the early detection of lesions.     

Esophageal squamous carcinoma

Squamous cell carcinoma of the esophagus is a tumor with poor prognosis; it is usually in an advanced state when first diagnosed. Because a multimodal treatment approach is currently used, proper tumor staging is essential to determine whether therapy should be directed toward cure or palliation. Important prognostic features of squamous cell carcinoma include the depth of tumor infiltration into or through the esophageal wall and the presence of distant metastases. Imaging strategies should not be limited to visualization of the tumor but also should be directed toward accurate pretreatment staging. In this article, the authors review the use of barium swallow, CT scans, and endoscopic ultrasonography both alone and in combination to visualize and stage esophageal carcinoma. The strengths and limitations of each modality are also discussed.     

Urinary nuclear matrix protein as a marker for transitional cell carcinoma of the urinary tract

PURPOSE: The purpose of this trial was to evaluate an immunoassay for urinary nuclear matrix protein, NMP22, as an indicator for transitional cell carcinoma of the urinary tract. MATERIALS AND METHODS: Three groups of subjects participated in this trial of NMP22: 1-175 with transitional cell carcinoma, 2-117 with benign urinary tract conditions and 3-375 healthy volunteers. Each subject provided a single (3 voids) urine sample for analysis at the time of study entry. Each sample was assayed for the level of NMP22. RESULTS: In normal healthy volunteers and in subjects with benign conditions median NMP22 levels were 2.9 and 3.3 units per ml., respectively. Median urinary NMP22 levels in patients with transitional cell carcinoma were significantly greater than in comparison subjects. Patients with active transitional cell carcinoma had significantly greater median urinary NMP22 levels than those with no evidence of disease (6.04 versus 4.11 units per ml., p = 0.027, 1-tailed Mann-Whitney U test). We noted no effect of tumor grade, extent of disease or exposure to intravesical therapy on urinary NMP22 levels. CONCLUSIONS: NMP22 is a promising urinary tumor marker for monitoring transitional cell carcinoma. Nuclear matrix proteins are a new class of tumor markers that represent the basis for the development of assays with increased efficacy for the detection and treatment of cancer.     

Endometrial cancer

Carcinoma of the uterine corpus (endometrial cancer) remains the gynecologic malignant disease with the highest annual prevalence in the United States. The most common histologic type is adenocarcinoma, although more aggressive variants (e.g., papillary serous carcinoma and clear cell carcinoma) have been identified. Risk factors that are strongly associated with the development of endometrial cancer include tamoxifen therapy, obesity, and stimulation from unopposed estrogen (from exogenous sources or endogenously secreting ovarian tumors). The current staging system of the International Federation of Gynecology and Obstetrics is based on surgical-pathologic findings. Survival has been directly correlated with tumor stage in this staging system. The cornerstone of therapy is total abdominal hysterectomy with bilateral salpingo-oophorectomy. Pelvic and para-aortic lymphadenectomy may provide additional prognostic information but probably does not confer a therapeutic advantage. Moreover, such nodal dissections predispose to the development of complications, especially in women who subsequently receive pelvic irradiation. Other than surgical treatment, irradiation is the single most active therapy for endometrial carcinoma. In fact, some women who are not candidates for hysterectomy because of medical contra-indications can be cured with radiation alone. Adjuvant therapy following hysterectomy is based on patient- and tumor-related features that provided prognostic information for incidence and pattern of recurrence. Adjuvant treatment usually includes pelvic irradiation for selected patients. Current investigational strategies are directed at the role of whole-abdomen irradiation, extended-field irradiation, and systemic chemotherapy. The most active systemic agents include cisplatin, doxorubicin, paclitaxel, and progestins.