Clustering of esophageal cancer among white men in the United States.

Studies of the geographic distribution of esophageal cancer in the United States have been limited. We aimed to examine geographic clustering of esophageal cancer in the United States and assess whether that clustering is explained by the distribution of known risk factors for esophageal cancer. We conducted cluster analyses derived from county mortality rates of esophageal cancer, using publicly available datasets. State incidence rates of esophageal adenocarcinoma were from the National Program of Cancer Registries, and county esophageal-cancer mortality rates were from the Vital Statistics Cooperative Program. County prevalences of cigarette use, alcohol use, obesity, education, and income were published estimates derived from the Behavioral Risk Factor Surveillance System and the American Community Survey. The primary outcomes were clusters of high and low esophageal-cancer mortality rates among non-Hispanic white men, both unadjusted and adjusted for risk factors. Age-standardized county rates of esophageal-cancer mortality among non-Hispanic white men ranged from 4.8 to 21.2 per 100,000/year. There was a cluster of high mortality in the Great Lakes states and New England and a cluster of low mortality in the Southeastern United States. State incidence rates of esophageal adenocarcinoma were consistent with this pattern. Adjusting for risk factors did little to change the pattern of observed rates or the clusters derived from them. Among non-Hispanic white men, there are clusters of high and low mortality rates with esophageal cancer within the United States, likely representing esophageal adenocarcinoma; but those clusters were not explained by several known risk factors. Focusing future efforts in the high-cluster areas might improve the efficiency of cancer screening and control.

Systematic review and meta-regressions: management of eosinophilic esophagitis requires histologic assessment.

Treatment endpoints in eosinophilic esophagitis (EoE) are response of eosinophilic inflammation and of symptoms. Steroids and diet therapy are effective in inducing histologic response in EoE, but there may be poor correlation between histologic and symptomatic response. Despite this, we find that in clinical practice symptoms are commonly used to guide management without assessing histologic response. We hypothesized that symptom response alone is not reliable in assessing response to therapy and is confounded by endoscopic dilation. We conducted a systematic review and meta-regressions to estimate the association of histologic and symptomatic response, stratified by whether concurrent dilation was permitted. We performed a systematic search of PubMed, EMBASE, and Web of Science for studies describing both histologic and symptomatic responses to dilation, steroid, and diet therapies. We abstracted the proportion of histologic response and symptom response. Studies were stratified by whether dilation was permitted. We performed meta-regressions of the association between the proportions with histologic and symptomatic response, stratified by whether dilation was permitted. We identified 1359 articles, of which 62 articles were assessed for eligibility, and 23 were included providing data on 1202 patients with EoE. Unstratified meta-regression of histologic versus symptomatic response showed moderate association and large heterogeneity (inconsistency index [I2] = 89%). In adult studies in which dilation was allowed, there was weak association between symptomatic and histologic response (ß1 = 0.21), minimal symptomatic response of 67% and the heterogeneity persisted, I2 = 77%. In studies that prohibited dilation, maximal symptomatic response was 72% and was moderately associated with histologic response (ß1 = 0.39) with less heterogeneity, I2 = 59%. Studies of EoE that permit dilation obscure the relation between histologic and symptomatic response and have a high floor effect for symptomatic response. Studies that prohibit dilation demonstrate moderate association between histologic and symptomatic response, but have a ceiling effect for symptomatic response. Our results demonstrate that success of dietary or medical management for EoE cannot be judged by symptoms alone, and require histologic assessment, particularly if dilation has been performed.

Prevalence and risk factors for heterotopic gastric mucosa of the upper esophagus among men undergoing routine screening colonoscopy.

The prevalence of heterotopic gastric mucosa of the upper esophagus (inlet patch) has a wide range depending on the method and detail of examination. The inlet patch is believed to be a congenital malformation that rarely leads to symptoms. We aimed to quantify the prevalence of the inlet patch in a non-referred population and determine if there are any risk factors or associated symptoms. Men between ages 50 and 79 presenting for routine colonoscopy at two clinical sites were recruited to undergo an upper endoscopy. Endoscopists were prompted to examine for the presence of the inlet patch. Of the 822 enrolled patients, 795 had data regarding the presence of an inlet patch. Of these, 55 (6.9%) had an inlet patch identified. Education was inversely associated (odds ratio [OR] advanced degree vs. high school or less = 0.310; 95% confidence interval [CI] = 0.111, 0.869), and tobacco use was positively associated with the presence of an inlet patch (current vs. never smokers OR = 2.87; 95% CI = 1.23, 6.69; former vs. never smokers OR = 1.93; 95% CI = 0.922, 4.02). No association between the inlet patch and symptoms of heartburn, globus, or dysphagia was found. In a cross-sectional study of colon cancer screenees, inlet patches were common and were not associated with symptoms. Tobacco use appears to be associated with the presence of an inlet patch.

Comparing trends in esophageal adenocarcinoma incidence and lifestyle factors between the United States, Spain, and the Netherlands.

OBJECTIVES: The incidence of esophageal adenocarcinoma (EAC) in the western world has been rapidly increasing. The trends in obesity and other lifestyle-associated factors have been hypothesized to be important drivers of this increase. We tested this hypothesis by comparing changes in these factors with changes in EAC incidence over time between three western countries. METHODS: Data on EAC incidence trends were abstracted from the SEER-9 registry (1975-2009) for the United States, from multiple cancer registries (1980-2004) in Spain, and from Eindhoven Cancer Registry in the Netherlands (1974-2010). In addition, we collected trend data on obesity, smoking, and alcohol consumption. The trend data were analyzed using log-linear regression. RESULTS: In 1980, the EAC incidence was similar among the three countries ((0.46-0.63) per 100,000). EAC incidence increased in all, with the largest increase observed in the Netherlands, followed by the United States and Spain (estimated annual percentage of change=9.7%, 7.4%, 4.3%, respectively). However, this pattern was not observed in lifestyle factors associated with EAC. With regards to obesity, the United States clearly has had the highest prevalence rates both in the past and in the present. For alcohol, the highest consumption rates are seen in Spain. Smoking showed a reverse trend compared with EAC among all three countries in the last 20 years. CONCLUSIONS: International trends in EAC incidence do not match corresponding trends in lifestyle-associated factors including obesity. Our findings suggest that factors other than obesity must be the important drivers for the increase in EAC incidence.

Association of adiponectin multimers with Barrett's oesophagus.

OBJECTIVE: Barrett's oesophagus is associated with abdominal obesity. Adiponectin is a peptide that is secreted from adipocytes and circulates in three multimeric forms: low molecular weight (LMW), middle molecular weight (MMW), and high molecular weight (HMW). The anti-inflammatory effects of adiponectin are specific to individual multimers, with LMW being most anti-inflammatory. We postulated that circulating levels of adiponectin and its multimers would be associated with the risk of Barrett's oesophagus. DESIGN: Cross-sectional study. SETTING: Outpatient clinic in North Carolina, USA. PATIENTS: Cases of Barrett's oesophagus and controls undergoing upper endoscopy for gastro-oesophageal reflux disease (GORD). MAIN OUTCOME MEASURES: Adjusted odds ratios of plasma adiponectin levels and its multimers for Barrett's oesophagus. RESULTS: There were 112 cases of Barrett's oesophagus and 199 GORD controls. Total adiponectin was not associated with Barrett's oesophagus (3(rd) tertile vs 1(st) tertile adjusted odds ratio (aOR) = 0.88; 95% confidence interval (CI) = 0.44 to 1.78). High levels of LMW adiponectin were associated with a decreased risk of Barrett's oesophagus (3(rd) tertile vs 1(st) tertile aOR = 0.33; 95% CI, 0.16 to 0.69), and a high LMW/total ratio appeared particularly inversely associated with Barrett's oesophagus (3(rd) tertile vs 1(st) tertile aOR = 0.27; 95% CI, 0.13 to 0.58). CONCLUSIONS: High levels of LMW adiponectin are associated with a decreased risk of Barrett's oesophagus among patients with GORD. Further human studies are required to confirm these findings, and in vitro studies are needed to understand if there is a mechanism whereby adiponectin may affect Barrett's metaplasia.

Oesophageal hypersensitivity is associated with features of psychiatric disorders and the irritable bowel syndrome.

BACKGROUND: Twenty per cent of patients with heartburn do not respond to proton pump inhibitors (PPIs). Many have normal oesophageal acid exposure. We hypothesized that such PPI non-responders have heightened oesophageal sensation, and that oesophageal hypersensitivity is associated with psychiatric features including somatization and anxiety. AIM: To compare oesophageal sensation in subjects with heartburn categorized by response to PPI, and to correlate oesophageal sensation with psychiatric features. METHODS: Twenty-one PPI responders, nine PPI non-responders and 20 healthy volunteers completed questionnaires of psychiatric disorders and gastrointestinal symptoms. Subjects underwent oesophageal sensory testing with acid perfusion and balloon distension. RESULTS: Healthy volunteers displayed higher thresholds for sensation and discomfort from balloon distension than heartburn subjects (sensation P = 0.04, discomfort P = 0.14). Psychiatric disorders were associated with increased intensity of sensation (P = 0.02) and discomfort from acid (P = 0.01). Somatization was associated with increased discomfort from balloon distension (P = 0.006). Features of irritable bowel syndrome were associated with increased sensation and discomfort. CONCLUSIONS: Heartburn subjects tend to have heightened oesophageal sensation, suggesting that oesophageal hypersensitivity may persist despite therapy with PPI. Oesophageal hypersensitivity is associated with features of psychiatric disease and with the irritable bowel syndrome, which might partly explain the aetiology of heartburn symptoms that are refractory to PPI.

Bolus clearance in esophagogastric junction outflow obstruction is associated with strength of peristalsis.

BACKGROUND: A manometric diagnosis of esophagogastric junction outflow obstruction (EGJOO) without a mechanical cause creates a therapeutic conundrum. The aim of this study was to assess esophageal bolus clearance in EGJOO and assess manometric factors associated with clearance in EGJOO. METHODS: Bolus clearance was assessed using line-tracing method and contour method to determine Complete Bolus Transit (CBT) and Functional Clearance (FC), respectively, on combined High-Resolution Impedance Manometry (HRIM). HRIM studies of EGJOO patients, as well as a sample of achalasia types I-III and asymptomatic controls, were retrospectively analyzed. In EGJOO, associations between Integrated Relaxation Pressure (IRP) or Distal Contractile Integral (DCI) and clearance were assessed using receiver-operating-characteristic (ROC) curves. KEY RESULTS: Seventy-five EGJOO, 28 achalasia, and 11 normal subjects were included. Agreement between CBT and FC was good (Kappa=0.75). CBT across swallows in each group was as follows: type I achalasia: 14%, type II achalasia: 8%, type III achalasia: 61%, EGJOO: 86%, and normal: 98% (p values .023, .006, and <.0001 for EGJOO vs normals, type III achalasia, and all achalasia, respectively). In idiopathic EGJOO, CBT ≥60% of swallows was seen in 96.4% of patients when mean DCI>610 mmHg-s-cm (accuracy 87.7%, P=.004). Complete Bolus Transit( CBT) across individual swallows was 97.8% when DCI>884 mmHg-s-cm (accuracy 81.9%, P<.0001). IRP was poorly associated with bolus clearance. CONCLUSIONS & INFERENCES: Bolus clearance in EGJOO is impaired compared to normal, but not as severely as in achalasia. In idiopathic EGJOO, weak peristalsis is associated with poor bolus clearance. Bolus transit appears to be unimpaired when DCI>900 mmHg-s-cm.

The cost-effectiveness of biomarkers for predicting the development of oesophageal adenocarcinoma.

BACKGROUND: The recommended surveillance strategy for oesophageal adenocarcinoma may prevent as few as 50% of cancer deaths. Tissue biomarkers have been proposed to identify high-risk patients. AIM: To determine performance characteristics of an ideal biomarker, or panel of biomarkers, that would make its use more cost-effective than the current surveillance strategy. METHODS: We created a Markov model using data from published literature, and performed a cost-utility analysis. The population consisted of 50-year-old Caucasian men with gastro-oesophageal reflux, who were monitored until age 80. We examined strategies of observation only, current practice (dysplasia-guided surveillance), surveillance every 3 months for patients with a positive biomarker (biomarker-guided surveillance), and oesophagectomy immediately for a positive biomarker (biomarker-guided oesophagectomy). The primary outcome was the threshold cost and performance characteristics needed for a biomarker to be more cost-effective than current practice. RESULTS: Regardless of the cost, the biomarker needs to be at least 95% specific for biomarker-guided oesophagectomy to be cost-effective. For biomarker-guided surveillance to be cost-effective, a $100 biomarker could be 80% sensitive and specific. CONCLUSIONS: Biomarkers predicting the development of oesophageal adenocarcinoma would need to be fairly accurate and inexpensive to be cost-effective. These results should guide the development of biomarkers for oesophageal adenocarcinoma.

Relationship between diabetes mellitus and adenocarcinoma of the oesophagus and gastric cardia.

BACKGROUND: Obesity is a risk factor for adenocarcinomas of the oesophagus and gastric cardia. Diabetes mellitus might mediate that association. AIM: To estimate the risk of diabetes mellitus on the development of adenocarcinoma of distal oesophagus and gastric cardia beyond that of gastro-oesophageal reflux disease. METHODS: A case-control study was performed using a national administrative database of the Veterans Administration. RESULTS: A total of 311 cases of cancer and 10,154 controls were identified. Gender, age, and race were risks for cancer. Diabetes was diagnosed in 36% of cases, and 32% of controls (P = 0.15). Diabetic complications were diagnosed in 14% of cases and 13% of controls (P = 0.60). Multiple logistic regression confirmed the absence of an association between cancer and diabetes (odds ratio 1.1, 95% confidence interval 0.8-1.5) or diabetic complications (odds ratio 0.8, 95% confidence interval 0.6-1.3), adjusting for age, gender, and race. CONCLUSIONS: Within the limitations of this case-control study, there is no evidence of an association between diabetes and adenocarcinoma of the oesophagus or gastric cardia among US veterans with gastro-oesophageal reflux disease.

Prospective prediction of post-radiation therapy lung function using quantitative lung scans and pulmonary function testing.

Surgeons have made use of quantitative perfusion lung scanning (QS) and forced expiratory volume in one second (FEV1) to predict a patient's ability to tolerate lung resection. In this study QS and FEV1 were used to predict prospectively pulmonary function following lung irradiation (XRT). Twenty-two patients have had QS and FEV1 determined before XRT and at planned intervals post-XRT. Serial determination of lung function post-XRT allows comment on the temporal nature of the XRT effect on lung function. Seventeen patients had QS and FEV1 determined at an interval of 2-6 months post-irradiation with a drop in the groups mean FEV1 from 1.91 to 1.87L. or 2% during that interval. In the interval from 6-12 months post-XRT, 13 patients had studies with the groups mean FEV1 dropping from 1.79 to 1.58L or 12% of the original. In the interval from 12-18 months, 6 patients had a decline in mean FEV1 from 1.73 to 1.56L. or 10% of the original. In 22 patients a predicted final FEV1 was compared with a measured value at an interval from XRT. Fourteen of these determinations were at intervals greater than 6 months from the start of XRT and 6 at intervals of greater than 1 year. FEV1 was seen to drop during the follow-up intervals toward the predicted value. In only 2 patients did the final FEV1 drop below the predicted FEV1 and never by more than 0.12L. (6%). In summary, a method for predicting post-XRT pulmonary function using QS and FEV1 is described. Serial follow-up revealed a latent period followed by a late phase where FEV1 fell toward, but not significantly below, the predicted value. Such a determination can be of value in formulating a treatment plan for patients with significantly diminished pulmonary function.

Adenocarcinoma of the esophagus and esophago-gastric junction: the effects of single and combined modalities on the survival and patterns of failure following treatment.

One hundred sixty-five patients with localized adenocarcinomas of the esophagus or esophago-gastric (EG) junction were treated with surgery alone, radiation therapy alone, chemotherapy alone, surgery followed by post-operative radiation therapy, chemotherapy, or chemosensitized radiation therapy, and chemosensitized radiation therapy alone. Patients were retrospectively evaluated for survival, control of tumor within the mediastinum, post-operative swallowing function, patterns of failure, and treatment-related morbidity. Follow-up of survivors ranges from 9-88 months (median 23 months). Chemotherapy and radiation therapy as single modalities were associated with a recurrence rate of 100%. Combined modality therapy significantly reduced the risk of local recurrence in all patient groups. Chemosensitized radiation therapy alone reduced the local recurrence rate to 48%, and surgery followed by radiation therapy reduced the local failure rate to 24%. When chemotherapy or chemosensitization was added to surgery plus radiation, the risk was further reduced to 15%. The use of combined modality therapy was also found to extend the survival of patients without excessive toxicity. Median survival was shortest among the group treated with radiation alone (5 months) and intermediate among patients following chemosensitized radiation alone (10 months) or complete surgical resection alone (15 months). Patients treated with all three modalities had the longest median survival (21 months). Based on this experience, the optimum treatment of these patients appears to include aggressive attempts at surgical resection with chemosensitized radiation therapy. Excellent palliation can also be achieved in unresectable patients with chemosensitized radiation therapy with a smaller chance for long term survival.

Results of radiotherapy for thyroid ophthalmopathy.

Between October, 1978 and August, 1986, 35 patients with thyroid ophthalmopathy were treated with radiotherapy. Twenty-eight patients had treatment with corticosteroids prior to radiotherapy and either progressed on steroids or relapsed during tapering. Seven patients with contraindications to steroids were treated primarily with radiotherapy. After radiotherapy, 25 patients (71%) did not require any further steroids or orbital decompression and ten (29%) failed. Patients who required steroids or decompression for active disease after radiotherapy were considered treatment failures. A total of 14 (40%) patients required eye muscle or lid surgery for correction of stable soft tissue defects after radiotherapy, more commonly in patients treated with radiotherapy after steroids or decompression than those irradiated primarily; the median time between radiotherapy and surgery was 8 months (range 1-48). Various factors were examined for prognostic significance in predicting radiotherapy failure. Review of the interval between onset of eye disease and radiotherapy demonstrated that six of ten (60%) failures versus only five of 25 (20%) successful treatments received radiotherapy within 6 months of onset of eye disease. No relation between outcome and sex, age or hyperthyroid versus euthyroid Graves' disease was apparent. Radiotherapy has been used for patients with thyroid ophthalmopathy who failed steroids, decompression, or had steroid contraindications. Morbidity of radiotherapy was minimal and most patients were spared the morbidity of continued steroid therapy.

Local control in medically inoperable lung cancer: an analysis of its importance in outcome and factors determining the probability of tumor eradication.

PURPOSE: For patients who are medically unable to tolerate a surgical resection for technically resectable non-small-cell lung carcinoma, radiation therapy is an acceptable alternative. We report on the effect of achieving local control of the primary tumor on survival end-points, and analyze factors that may influence local control. METHODS AND MATERIALS: We reviewed the records of 152 patients with medically inoperable non-small-cell lung carcinoma treated at our institutions. All patients had technically resectable lesions and no evidence of metastatic disease. Treatment was delivered using megavoltage irradiation to doses ranging from 45 to 75 Gy. RESULTS: For patients with tumors 3 cm or less, locally controlling the tumor significantly improved survival (p = .0371). Patients with T1 tumors had a higher probability of survival and disease-free-survival than patients with larger tumors if the primary tumor was locally controlled, but this survival advantage disappeared if the tumor was not controlled. Overall, patients with smaller tumors had a lower incidence of distant spread, but this association was maintained only when the primary tumor was controlled (36 month risk of 10%, 23%, and 57% for tumors < 3 cm, 3-4.9 cm, 5 cm or greater, respectively, p = .0027). For patients whose tumors were not controlled, there was no significant difference in the risk of distant dissemination by tumor size. Higher radiation doses influenced local control and metastatic spread. We observed no influence of the initial field size in the risk of local control and in the probability of survival. CONCLUSION: Radical radiation therapy is an effective treatment for small (T1 or < 3 cm) tumors when treated to doses of 65 Gy or more, and should be offered as an alternative to surgery in elderly or infirm patients. New therapeutic strategies to improve the local control rate should be considered for larger tumors, through the use of hyperfractionated treatment, endobronchial "boost" irradiation, and sensitizing chemotherapy agents.

Low doses of prophylactic cranial irradiation effective in limited stage small cell carcinoma of the lung.

PURPOSE: Prophylactic cranial irradiation (PCI) for the prevention of brain metastasis in small cell lung cancer remains controversial, both in terms of efficacy and the optimal dose-fractionation scheme. We performed this study to evaluate the efficacy of PCI at low doses. METHODS AND MATERIALS: One hundred and ninety-seven patients were referred to our institution for treatment of limited stage small cell carcinoma of the lung between June 1986 and December 1992. Follow-up ranged from 1.1 to 89.8 months, with a mean of 19 months. Eighty-five patients received PCI. RESULTS: Patients receiving PCI exhibited brain failure in 15%, while 38% of untreated patients developed metastases. This degree of prophylaxis was achieved with a median total dose of 25.20 Gy and a median fraction size of 1.80 Gy. At these doses, acute and late complications were minimal. Patients receiving PCI had significantly better 1-year and 2-year overall survivals (68% and 46% vs. 33% and 13%). However, patients with a complete response (CR) to chemotherapy and better Karnofsky performance status (KPS) were overrepresented in the PCI group. In an attempt to compare similar patients in both groups (PCI vs. no PCI), only patients with KPS > or = 80, CR or near-CR to chemotherapy, and treatment with attempt to cure, were compared. In this good prognostic group, survival was still better in the PCI group (p = 0.0018). CONCLUSION: In this patient population, relatively low doses of PCI have accomplished a significant reduction in the incidence of brain metastasis with little toxicity. Whether such treatment truly improves survival awaits the results of additional prospective randomized trials.

Radiation therapy in the management of medically inoperable carcinoma of the lung: results and implications for future treatment strategies.

Surgery is the treatment of choice for resectable non-small cell lung carcinoma. For patients who are medically unable to tolerate a surgical resection or who refuse surgery, radiation therapy is an acceptable alternative. We reviewed the records of 152 patients with medically inoperable non-small cell lung carcinoma treated at our institution between 1982 and 1990. Patients with metastatic disease, mediastinal lymph node involvement or unresectable tumors were excluded. The actuarial overall survival at 2 and 5 years was 40% and 10%, respectively. The disease-free survival at 2 and 5 years was 31% and 15%. The disease-free survival for patients with T1 tumors was 55% at 2 years, versus 20 and 25% for T2 and T3 lesions, respectively (p = .0006). Increasing tumor dose was also associated with increasing disease-free survival (p = .0143). Overall, 66% percent of the patients were considered to have failed. Of these, 70% showed a component of local failure and 45% failed distantly. Patients with T1 tumors experienced a lower probability of failing locally or distantly than did patients with T2 or T3 tumors. A reduced risk of local and distant failure was seen for patients treated to doses of greater than 65 Gray, especially for T1 tumors. We conclude that radical radiation therapy is an effective treatment for small tumors when treated to doses of 65 Gray or more. Since local failure is the prominent pattern of relapse in patients with large tumors, new therapeutic strategies should be considered for this patient group.

Effective palliative radiation therapy in advanced and recurrent ovarian carcinoma.

PURPOSE: To retrospectively review our experience using radiation therapy as a palliative treatment in ovarian carcinoma. METHODS AND MATERIALS: Eighty patients who received radiation therapy for ovarian carcinoma between 1983 and 1998 were reviewed. The indications for radiation therapy, radiation therapy techniques, details, tolerance, and response were recorded. A complete response required complete resolution of the patient's symptoms, radiographic findings, palpable mass, or CA-125 level. A partial response required at least 50% resolution of these parameters. The actuarial survival rates from initial diagnosis and from the completion of radiation therapy were calculated. RESULTS: The median age of the patients was 67 years (range 26 to 90 years). A median of one laparotomy was performed before irradiation. Zero to 20 cycles of a platinum-based chemotherapy regimen were delivered before irradiation (median = 6 cycles). The reasons for palliative treatment were: pain (n = 22), mass (n = 23), obstruction of ureter, rectum, esophagus, or stomach (n = 12), a positive second-look laparotomy (n = 9), ascites (n = 8), vaginal bleeding (n = 6), rectal bleeding (n = 1), lymphedema (n = 3), skin involvement (n = 1), or brain metastases with symptoms (n = 11). Some patients received treatment for more than one indication. Treatment was directed to the abdomen or pelvis in 64 patients, to the brain in 11, and to other sites in 5. The overall response rate was 73%. Twenty-eight percent of the patients experienced a complete response of their symptoms, palpable mass, and/or CA-125 level. Forty-five percent had a partial response. Only 11% suffered progressive disease during therapy that required discontinuation of the treatment. Sixteen percent had stable disease. The duration of the responses and stable disease lasted until death except in 10 patients who experienced recurrence of their symptoms between 1 and 21 months (median = 9 months). The 1-, 2-, 3-, and 5-year actuarial survival rates from diagnosis were 89%, 73%, 42%, and 33%, respectively. The survival rates calculated from the completion of radiotherapy were 39%, 27%, 13%, and 10%, respectively. Five percent of patients experienced Grade 3 diarrhea, vomiting, myelosuppression, or fatigue. Fourteen percent of patients experienced Grade 1 or 2 diarrhea, 19% experienced Grade 1 or 2 nausea and vomiting, and 11% had Grade 1 or 2 myelosuppression. CONCLUSIONS: In this series of radiation therapy for advanced ovarian carcinoma, the response, survival, and tolerance rates compare favorably to those reported for current second- and third-line chemotherapy regimens. Cooperative groups should consider evaluating prospectively the use of radiation therapy before nonplatinum and/or nonpaclitaxel chemotherapy in these patients.

Systematic review: the hepatotoxicity of non-steroidal anti-inflammatory drugs.

BACKGROUND: Non-steroidal anti-inflammatory drugs have been implicated in reports of liver injury. However, the precise risk of non-steroidal anti-inflammatory drugs for this rare complication is unknown. AIM: To review systematically the published literature of population-based epidemiological studies reporting the incidence or comparative risk of non-steroidal anti-inflammatory drugs for liver injury resulting in clinically significant events, defined as hospitalization or death. DATA EXTRACTION: Duplicate extraction of the methodological quality, design, source, population, years studied, particular non-steroidal anti-inflammatory drugs studied, definitions, patient counts and follow-up, and the adjustment for confounders. RESULTS: Seven articles met inclusion criteria. The comparative risk of liver injury resulting in hospitalization for current non-steroidal anti-inflammatory drug users compared with past non-steroidal anti-inflammatory drug users ranged from 1.2 to 1.7, but none was statistically significant. The incidence of liver injury resulting in hospitalization ranged from 3.1 to 23.4/100,000 patient-years of current use of non-steroidal anti-inflammatory drugs, with an excess risk compared with past non-steroidal anti-inflammatory drugs users of 4.8-8.6/100,000 patient-years of exposure. There were zero deaths from liver injury associated with non-steroidal anti-inflammatory drugs use in over 396,392 patient-years of cumulative exposure. CONCLUSION: These findings allow for the possibility of a small increase in the risk of clinically relevant hepatotoxicity with non-steroidal anti-inflammatory drugs use, but do not document that such a risk occurs.

Small cell anaplastic carcinoma of the prostate: seven new cases, review of the literature, and discussion of a therapeutic strategy.

Small cell anaplastic carcinoma of the prostate (SCCP) is a rare entity; a literature review disclosed fewer than 150 cases. SCCP has an aggressive course, and both local and distant failure is common. The optimal treatment method has not been clearly established. We review our experience with 7 patients, with attention paid to clinical and pathological details based on a review of the histological specimens. Three patients had mixed tumors of both SCCP and adenocarcinoma, 3 had pure adenocarcinomas that recurred as small cell, and 1 had pure small cell. Our series confirms the aggressive nature of the disease, with all patients dying of their disease < or = 42 months after diagnosis. All patients progressed locally, and at least 5 later developed distant metastases. Treatment with combination chemotherapy and/or hormones resulted in short-lived responses in most patients. We recommend use of hormonal manipulation and combination chemotherapy as well as surgery and/or radiation therapy to the prostate for local control and emphasize that histologic recognition of the entity is important for proper treatment.

Small-cell lung carcinoma: an analysis of 194 consecutive patients.

The treatment of small-cell lung carcinoma (SCLC) requires the careful combination of chemotherapy and radiation therapy. To understand the factors involved in the outcome of these patients, the authors undertook a study of patients treated for limited stage SCLC. The charts of 194 consecutive patients treated at our facilities between 1986 and 1994 were reviewed. All patients underwent thoracic radiation therapy (TRT), 50% received prophylactic cranial irradiation (PCI), and all but one received chemotherapy. The probability of survival at 5 years was 14%, and the disease-free survival (DFS) was 17%. Patients receiving a combination of platinum and etoposide (PE) and Cytoxan (Bristol-Myers, Evansville, IN, U.S.A.), Adriamycin (Adria Laboratories, Dublin, OH, U.S.A.), and Vincristine (Eli Lilly, Indianapolis, IN, U.S.A.) (CAV) experienced a DFS at 3 years of 31%, versus 14% for CAV only and 18% for PE only (p = 0.004). In a multivariate survival analysis, only PCI (p = 0.001), having received PE and CAV (p = 0.01), and response to treatment (p = 0.001) were significant. Radiation dose and field size did not influence outcome. The combination of PE and CAV chemotherapy produced the best results in our series. Unanswered questions regarding the optimal TRT dose, field size, and timing of TRT await the results of ongoing randomized trials.