Prognosis in HIV-infected patients with non-small cell lung cancer.

BACKGROUND: We conducted a population-based study to evaluate whether non-small cell lung cancer (NSCLC) prognosis was worse in HIV-infected compared with HIV-uninfected patients. METHODS: Using the Surveillance, Epidemiology and End Results (SEER) registry linked to Medicare claims, we identified 267 HIV-infected patients and 1428 similar controls with no evidence of HIV diagnosed with NSCLC between 1996 and 2007. We used conditional probability function (CPF) analyses to compare survival by HIV status accounting for an increased risk of non-lung cancer death (competing risks) in HIV-infected patients. We used multivariable CPF regression to evaluate lung cancer prognosis by HIV status adjusted for confounders. RESULTS: Stage at presentation and use of stage-appropriate lung cancer treatment did not differ by HIV status. Median survival was 6 months (95% confidence interval (CI): 5-8 months) among HIV-infected NSCLC patients compared with 20 months (95% CI: 17-23 months) in patients without evidence of HIV. Multivariable CPF regression showed that HIV was associated with a greater risk of lung cancer-specific death after controlling for confounders and competing risks. CONCLUSION: NSCLC patients with HIV have a poorer prognosis than patients without evidence of HIV. NSCLC may exhibit more aggressive behaviour in the setting of HIV.

Staging of pancreatic cancer with multidetector CT in the setting of preoperative chemoradiation therapy.

BACKGROUND: Preoperative chemoradiation can potentially improve outcomes in patients with pancreatic cancer. This study addresses its effect on staging pancreatic cancer with multidetector computed tomography (MDCT). METHODS: Fifty-five patients underwent a dual-phase MDCT pancreas protocol for proved pancreatic cancer. Of these, 16 patients underwent preoperative chemoradiation. Three radiologists independently reviewed images to assess for locally advanced disease, liver and peritoneal metastases on baseline studies of all 55 patients, and on follow-up preoperative studies for the 16 patients receiving preoperative therapy. Overall score for resectability was graded on a scale from 1 to 5 (1, definitely resectable; 5. definitely unresectable). Receiver operating characteristic curves and weighted (kappa statistics were determined. RESULTS: The areas under the receiver operating characteristic curves for readers 1, 2, and 3 were 0.98, 0.96, and 0.90, respectively. Weighted kappa values for reader 1 versus reader 2, reader 1 versus reader 3, and reader 2 versus reader 3 were 0.90, 0.57, and 0.54, respectively. Interpreting scores of 1 to 3 for resectability as resectable disease, the mean values for sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 0.92, 0.91, 0.74, 0.98, and 0.92 respectively. CONCLUSION: The negative predictive value for MDCT for identifying unresectable pancreatic cancer in the setting of preoperative therapy is comparable to that reported in the absence of neoadjuvant therapy.

Imaging of esophageal cancer.

Esophageal cancer is a relatively uncommon gastrointestinal malignancy but carries a poor prognosis unless it is of early stage and can be surgically resected for cure. Resectability is determined by the stage of disease at diagnosis and therefore accurate staging is of importance in patients diagnosed with esophageal cancer. Imaging studies that play a role in the evaluation of esophageal cancer include barium studies, computed tomography, endoscopic ultrasound and positron emission tomography. Imaging provides important information regarding the local extent and any distant spread of disease, which in turn helps in determining optimal management for these patients. This review discusses the imaging findings that may be encountered with various imaging modalities in the diagnosis, staging and follow-up of esophageal cancer.

Radio-frequency ablation of liver tumors: assessment of therapeutic response and complications.

An alternative to surgical resection of liver tumors, radio-frequency ablation induces in situ thermal coagulation necrosis through the delivery of high-frequency alternating current to the tissues. Imaging helps to detect treatable lesions, guide the placement of the probe, and assess the effect of therapy. Computed tomography (CT) is used most frequently to determine whether the ablation is complete and to screen for early recurrences that may benefit from reablation. Complete ablation creates an area of necrosis that, at CT, is of low attenuation compared with the surrounding liver tissue, is often homogeneous, and has smooth margins. The most important features are the size of the necrotic defect, which, immediately after treatment, should be larger than that of the pretreatment tumor, and the sharpness of the margins, which indicates an abrupt change in attenuation between the necrotic tissue and surrounding liver tissue. Enhancement, when present, is due to perfusion abnormality or granulation tissue and forms a regular rim or a homogeneous zone at the margin of the defect. It is seen immediately after ablation but may be prolonged. Enhancement is affected by the scanning technique. Over time, the size of the defect remains stable or decreases. Any variation from this general pattern is suggestive of incomplete ablation or recurrence.

Elective groin irradiation is not indicated for patients with adenocarcinoma of the rectum extending to the anal canal.

PURPOSE: To evaluate the inguinal nodal failure rate in patients with locally advanced rectal cancer with anal canal involvement (ACI) treated with pelvic chemoradiation without elective inguinal irradiation. METHODS AND MATERIALS: From 1990 and 1998, 536 patients received preoperative or postoperative chemoradiation for rectal cancer with curative intent; 186 patients had ACI (<4 cm from the anal verge on rigid proctoscopy). Two patients had positive inguinal nodes at presentation. Chemoradiation was delivered preoperatively (45 Gy in 25 fraction) or postoperatively (53 Gy in 29 fractions) with concurrent continuous infusion of 5-fluorouracil (300 mg/m2/d). The inguinal region was specifically irradiated in only 2 patients who had documented inguinal nodal disease. RESULTS: The median follow-up was 50 months. Only 6 of 184 ACI patients who had clinically negative inguinal nodes at presentation developed inguinal nodal recurrence (5-year actuarial rate 4%); 4 of the 6 cases were isolated. Two patients underwent successful salvage. Only 1 died of uncontrolled groin disease. Local control was achieved in both patients with inguinal nodal disease at presentation, but both died of metastatic disease. Only 3 patients with tumors >4 cm from the verge developed inguinal recurrence (5-year actuarial rate <1%). CONCLUSIONS: Inguinal nodal failure in rectal cancer patients with ACI treated with neoadjuvant or adjuvant chemoradiation is not high enough to justify routine elective groin irradiation.

Nutrient intake and risk of subtypes of esophageal and gastric cancer.

Incidence rates for adenocarcinoma of the esophagus and gastric cardia have been rising rapidly. We examined nutrient intake as a risk factor for esophageal and gastric cancers in a population-based case-control study in Connecticut, New Jersey, and western Washington state. Interviews were completed for cases with histologically confirmed esophageal adenocarcinoma (n = 282), adenocarcinoma of the gastric cardia (n = 255), esophageal squamous cell carcinoma (n = 206), and noncardia gastric adenocarcinoma (n = 352), along with population controls (n = 687). Associations between nutrient intake and risk of cancer were estimated by adjusted odds ratios (ORs), comparing the 75th versus the 25th percentile of intake. The following nutrients were significantly inversely associated with risk of all four tumor types: fiber, beta-carotene, folate, and vitamins C and B6. In contrast, dietary cholesterol, animal protein, and vitamin B12 were significantly positively associated with risk of all four tumor types. Dietary fat [OR, 2.18; 95% confidence interval (CI), 1.27-3.76] was significantly associated with risk of esophageal adenocarcinoma only. Dietary nitrite (OR, 1.65; 95% CI, 1.26-2.16) was associated with noncardia gastric cancer only. Vitamin C supplement use was associated with a significantly lower risk for noncardia gastric cancer (OR, 0.60; 95% CI, 0.41-0.88). Higher intake of nutrients found primarily in plant-based foods was associated with a reduced risk of adenocarcinomas of the esophagus and gastric cardia, whereas higher intake of nutrients found primarily in foods of animal origin was associated with an increased risk.

Family history of cancer and risk of esophageal and gastric cancers in the United States.

The worldwide rates for histology- and subsite-specific types of esophageal and gastric cancer reveal strikingly divergent patterns. The contribution of environmental and genetic factors has been explored in several high-incidence areas, but data on genetic influences are scarce for Western countries. Using data from a multicenter, population-based, case-control study on 1,143 cases and 695 controls in the United States, we evaluated whether a family history of digestive or other cancers was associated with an increased risk of esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261) or non-cardia gastric adenocarcinoma (n = 368). After adjusting for other risk factors, individuals reporting a family history of digestive cancers experienced no increased risk of either type of esophageal cancer but they were prone to adenocarcinomas of the gastric cardia [odds ratio (OR) = 1.34, 95% confidence interval (CI) 0.91-1.97] and non-cardia segments (OR =1.46, 95% CI 1.03-2.08). This familial tendency, particularly for non-cardia gastric tumors, was largely explained by an association with family history of stomach cancer (OR = 2.52, 95% CI 1.50-4.23). In addition, family history of breast cancer was associated with increased risks of esophageal adenocarcinoma (OR = 1.74, 95% CI 1.07-2.83) and non-cardia gastric adenocarcinoma (OR = 1.76, 95% CI 1.09-2.82). Also seen were non-significant familial associations of esophageal squamous-cell cancer with prostate cancer as well as non-cardia gastric cancer with leukemia and brain tumors, though these relationships must be interpreted with caution. Our data point to the role of familial susceptibility to gastric cancer, but not to any form of esophageal cancer, in the United States.

Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer.

The aim of this study was to determine if the response to preoperative radiation and chemotherapy with continuous infusion 5-fluorouracil (5-FU) was predictive for survival among patients with locally advanced rectal cancer. Preoperative chemoradiation (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-FU (300 mg/m2/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/XRT, surgery was performed. Adjuvant chemotherapy, consisting of 400 to 425 mg/m2 of 5-FU plus 20 mg/m2 leucovorin for 5 days, was administered every 28 days for 4 to 6 cycles after surgical resection. Among the 74 patients treated with adjuvant chemotherapy, the preoperative stage of disease was 31 with T3N0 and 43 T3N1. Median follow-up was 46 months (range 2 to 89 months). The pathologic tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4N1 in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor down-staging occurred in 72 (62%) cases. A sphincter-saving procedure (SP) was possible in 59% of patients. The median DFS and overall survival rates for responders were 46 months and 47 months, respectively; for non-responders these outcome measures were 38 months and 41 months, respectively. Log-rank analysis showed that the distant metastatic-free survival rates improved with any response to CTX/XRT (p < 0.00001), CR to CTX/XRT (p < 0.009) and SP (p < 0.012). Likewise, these parameters also significantly influenced DFS rates (CTX/XRT p < 0.00001; CR p < 0.006; and SP p < 0.008). Control of pelvic disease was influenced by clinical size (p < 0.002) and SP (p < 0.016) on univariate analysis. On multivariate analysis only clinical size (p < 0.002) continued to be a significant factor for local control. Factors on multivariate analysis that resulted in significant improvements in cancer-specific survival included any response to preoperative CTX/XRT (p < 0.017) and administration of adjuvant chemotherapy (p < 0.034). Any response to preoperative CTX/XRT improved distant metastatic-free and disease-free survival rates. Multivariate analysis confirmed that a response to preoperative CTX/XRT predicted for improvements in overall survival among patients with locally advanced rectal cancer. Patients who fail to respond to preoperative 5-FU based chemotherapy given concomitantly with radiation have higher rates of distant metastases with adjuvant 5-FU therapy.

Effective pelvic symptom control using initial chemoradiation without colostomy in metastatic rectal cancer.

PURPOSE: To assess pelvic chemoradiotherapy (CXRT) without colostomy as a component of the multidisciplinary management of patients presenting with metastatic rectal cancer. METHODS AND MATERIALS: Eighty patients with synchronous distant metastases from rectal cancer were treated with initial CXRT. Hypofractionated radiotherapy was administered usually with concurrent 5-FU (92%, 300 mg/m(2)/day, M-F). Three-field belly-board technique was used in 89%. Group 1 had CXRT alone (n = 55). Group 2 (n = 25) patients were selected for primary disease resection, and sometimes HAI chemotherapy (n = 10) or hepatic resection (n = 5). Subsequently, 78% received systemic chemotherapy. RESULTS: Symptoms from primary tumor resolved in 94%. Endoscopic complete clinical response rate was 36%. Two-year survival (11% vs. 46%, p < 0.0001) and symptomatic pelvic control (PC, 81% vs. 91%, p = 0.111) were higher in Group 2, but colostomy-free rate (CFR) was lower (79% vs. 51% p = 0.02). CFR was 87% in Group 1 patients managed initially without fecal diversion (n = 50). Examining all patients using multivariate analysis, pelvic pain at presentation (p < 0.00001), BED (biologic equivalent dose at 2 Gy/fraction) < 35 Gy (p = 0.077), and poor differentiation (0.079) predicted worse PC. Poor differentiation (p = 0.017) and selection for CXRT alone (p < 0.0001) predicted worse survival. There were 4 RTOG of Grade 3 or greater acute complications, 5 severe perioperative complications, and no significant late treatment-related complications. CONCLUSION: Durable PC can be safely achieved without colostomy in most patients presenting with primary rectal cancer and synchronous systemic metastases using hypofractionated pelvic chemoradiation. A BED greater than 35 Gy is recommended. Selected patients appear to benefit from resection of primary disease. Higher doses should be investigated in patients with pelvic pain.

Oxychlordane and trans-nonachlor in breast adipose tissue and risk of female breast cancer.

BACKGROUND: Organochlorine compounds, including organochlorine pesticides, have been suggested by some, but not all, studies to be associated with female breast-cancer risk. So far, studies relating organochlorine compounds and breast-cancer risk have mainly focused on polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) as risk factors for female breast cancer. This paper examines the hypothesis that environmental exposure to trans-nonachlor (TNC) and oxychlordane (OCD), a major metabolite of the insecticide chlordane, increases the METHODS: A total of 304 histologically confirmed, incident primary breast-cancer patients and 186 histologically confirmed incident benign breast-disease controls were included in the study between 1994 and 1997. Breast adipose tissue not needed for diagnostic purposes was collected and analysed for TNC, OCD and other organochlorine compounds. A standardised, structured questionnaire was used to obtain information on major known, or suspected, risk factors for breast cancer. RESULTS: The age and lipid-adjusted geometric mean adipose-tissue levels of OCD were similar between the cases [36.4 p.p.b., 95% confidence interval (CI) 34.7-38.2 p.p.b.] and controls (38.0 p.p.b., 95% Cl 35.7-40.6 p.p.b.). The age and lipid-adjusted geometric mean adipose-tissue levels of TNC between the cases (55.5 p.p.b., 95% CI 52.6-58.5 p.p.b.) and controls (58.1 p.p.b., 95% CI 54.2-62.3 p.p.b.) were also similar. There was no association between breast-cancer risk and mean adipose-tissue levels of OCD and TNC. The covariate-adjusted odds ratio (OR) was 0.7 (95% CI 0.4-1.3) for OCD and 1.1 (95% CI 0.6-1.9) for TNC, when the highest quartile was compared with the lowest. The risk also did not vary based on oestrogen or progesterone receptor status or menopausal status. DISCUSSION: We found no significantly increased risk of breast cancer associated with breast adipose-tissue levels of OCD or TNC; this is consistent with recent epidemiological studies, indicating that environmental exposure to organochlorine compounds does not have an overall significant impact on breast-cancer risk.

Breast cancer risk associated with congeners of polychlorinated biphenyls.

Experimental studies show that hormonal and nonhormonal activities of polychlorinated biphenyls (PCBs) are structure dependent, suggesting that the breast cancer risk associated with PCBs may vary according to specific PCB congeners. In 1994-1997, the authors conducted a case-control study of Connecticut women to investigate whether breast cancer risk is associated with body burden of PCBs and varies by PCB congeners. A total of 304 breast cancer cases and 186 controls aged 40-79 years were recruited into the study. Fresh breast adipose tissue was analyzed for PCBs. The age- and lipid-adjusted geometric mean tissue levels of total PCBs were not significantly different (p = 0.46) for the cases (478.6 parts per billion) and controls (494.1 parts per billion). The covariate-adjusted odds ratio was 0.7 (95% confidence interval: 0.4, 1.1) for all study participants when the third tertile was compared with the lowest tertile. No individual congeners or groups of congeners were associated with a significantly increased risk of breast cancer. Further stratification by type of breast disease; menopausal, parity, and lactation status; and body size also showed no significant association with body levels of PCBs. These results suggest that environmental exposure to PCBs may not substantially affect breast cancer risk.

Prospective trial of preoperative concomitant boost radiotherapy with continuous infusion 5-fluorouracil for locally advanced rectal cancer.

RATIONALE: To evaluate the response to a concomitant boost given during standard chemoradiation for locally advanced rectal cancer. METHODS AND MATERIALS: Concomitant boost radiotherapy was administered preoperatively to 45 patients with locally advanced rectal cancer in a prospective trial. Treatment consisted of 45 Gy to the pelvis with 18 mV photons at 1.8 Gy/fraction using a 3-field belly board technique with continuous infusion 5FU chemotherapy (300mg/m(2)) 5 days per week. The boost was given during the last week of therapy with a 6-hour inter-fraction interval to the tumor plus a 2-3 cm margin. The boost dose equaled 7.5 Gy/5 fractions (1.5 Gy/fraction); a total dose of 52.5 Gy/5 weeks was given to the primary tumor. Pretreatment tumor stage, determined by endorectal ultrasound and CT scan, included 29 with T3N0 [64%], 11 T3N1, 1 T3Nx, 2 T4N0, 1 T4N3, and 1 with TxN1 disease. Mean distance from the anal verge was 5 cm (range 0-13 cm). Median age was 55 years (range 33-77 years). The population consisted of 34 males and 11 females. Median time of follow-up is 8 months (range 1-24 months). RESULTS: Sphincter preservation (SP) has been accomplished in 33 of 42 (79%) patients resected to date. Three patients did not undergo resection because of the development of metastatic disease in the interim between the completion of chemoradiation (CTX/XRT) and preoperative evaluation. The surgical procedures included proctectomy and coloanal anastomosis (n = 16), low anterior resection (n = 13), transanal resection (n = 4). Tumor down-staging was pathologically confirmed in 36 of the 42 (86%) resected patients, and 13 (31%) achieved a pathologic CR. Among the 28 tumors (67%) located <6 cm from the anal verge, SP was accomplished in 21 cases (75%). Although perioperative morbidity was higher, toxicity rates during CTX/XRT were comparable to that seen with conventional fractionation. Compared to our contemporary experience with conventional CTX/XRT (45Gy; 1.8 Gy per fraction), improvements were seen in SP (79% vs. 59%; p = 0.02), SP for tumors <6 cm from the anal verge (75% vs. 42%; p = 0.003), and down-staging (86% vs. 62%; p = 0.003). CONCLUSION: The SP rate with concomitant boost radiation has been highly favorable with rates of response which are higher than those previously reported for chemoradiation without administration of a boost. Further evaluation of this radiotherapeutic strategy appears warranted.

Gastroesophageal reflux disease, use of H2 receptor antagonists, and risk of esophageal and gastric cancer.

OBJECTIVE: The incidence of esophageal adenocarcinoma has risen rapidly in the past two decades, for unknown reasons. The goal of this analysis was to determine whether gastroesophageal reflux disease (GERD) or the medications used to treat it are associated with an increased risk of esophageal or gastric cancer, using data from a large population-based case-control study. METHODS: Cases were aged 30-79 years, newly diagnosed with esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261), or non-cardia gastric adenocarcinoma (n = 368) in three areas with population-based tumor registries. Controls (n = 695) were chosen by random digit dialing and from Health Care Financing Administration rosters. Data were collected using an in-person structured interview. RESULTS: History of gastric ulcer was associated with an increased risk of non-cardia gastric adenocarcinoma (OR 2.1, 95% CI 1.4-3.2). Risk of esophageal adenocarcinoma increased with frequency of GERD symptoms; the odds ratio in those reporting daily symptoms was 5.5 (95% CI 3.2-9.3). Ever having used H2 blockers was unassociated with esophageal adenocarcinoma risk (OR 0.9, 95% CI 0.5-1.5). The odds ratio was 1.3 (95% CI 0.6-2.8) in long-term (4 or more years) users, but increased to 2.1 (95% CI 0.8-5.6) when use in the 5 years prior to the interview was disregarded. Risk was also modestly increased among users of antacids. Neither GERD symptoms nor use of H2 blockers or antacids was associated with risk of the other three tumor types. CONCLUSIONS: Individuals with long-standing GERD are at increased risk of esophageal adenocarcinoma, whether or not the symptoms are treated with H2 blockers or antacids.

Risk of female breast cancer associated with serum polychlorinated biphenyls and 1,1-dichloro-2,2'-bis(p-chlorophenyl)ethylene.

This case-control study was designed to investigate the relationship between polychlorinated biphenyls (PCBs) and 1,1-dichloro-2,2'-bis(p-chlorophenyl)ethylene (DDE) and breast cancer risk in Connecticut. Cases were incident breast cancer patients who were either residents of Tolland County or who had a breast-related surgery at the Yale-New Haven Hospital in New Haven County. Controls were randomly selected from Tolland County residents or from patients who had newly diagnosed benign breast diseases or normal tissue at Yale-New Haven Hospital. A total of 475 cases and 502 controls had their serum samples analyzed for PCBs and DDE in 1995-1997. The age- and lipid-adjusted geometric mean serum level of DDE was comparable between the cases (460.1 ppb) and controls (456.2 ppb). The geometric mean serum level of PCBs was also comparable between cases (733.1 ppb) and controls (747.6 ppb). After adjustment for confounding factors, odds ratios of 0.96 (95% confidence interval, 0.67-1.36) for DDE and 0.95 (95% confidence interval, 0.68-1.32) for PCBs were observed when the third tertile was compared with the lowest. Further stratification by parity, lactation, and menopausal and estrogen receptor status also showed no significant association with serum levels of DDE or PCBs. The results by PCB congener groups also showed no major increased risk associated with any of the congener groups. Our study does not support the hypothesis that DDE and PCBs, as encountered through environmental exposure, increase the risk of female breast cancer.

Colitis associated with docetaxel-based chemotherapy in patients with metastatic breast cancer.

BACKGROUND: Docetaxel and vinorelbine as combined treatment for metastatic breast cancer can have the dose-limiting toxic effects of mucositis and neutropenic fever. We report unexpected ischaemic colitis in six patients associated with docetaxel-based therapy, three of whom were treated in a phase I study designed to establish the maximum tolerated dose of this combination with the prophylactic use of granulocyte-colony-stimulating factor. METHODS: Between August, 1997, and December, 1998, 14 patients with metastatic breast cancer were treated with vinorelbine, docetaxel, and granulocyte-colony-stimulating factor in a phase I study. Three patients developed colitis similar to that seen in typhlitis. Three additional patients were identified during scheduled review of toxic effects in patients participating in clinical trials involving docetaxel. FINDINGS: Three patients on combined vinorelbine and docetaxel developed colitis-like symptoms. Two patients died, one from necrotic bowel and the other from neutropenic fever and colitis. Two of the patients presented on day 7 and day 8 of chemotherapy, respectively, with neutropenic fever and abdominal pain; the third patient developed neutropenia without fever and abdominal pain on day 8. The other three patients were treated with docetaxel, docetaxel and pamidronate disodium, or docetaxel and cyclophosphamide. All three patients presented with abdominal pain on days 10, 5, and 4, respectively. One had non-neutropenic fever, another had neutropenic fever, and the third was afebrile and non-neutropenic at the time of presentation with abdominal pain. Three patients had blood in their diarrhoea, abdominal tenderness, or both. Computed tomography of the abdomen and pelvis showed features of colitis in three patients. INTERPRETATION: This serious complication may result from the use of docetaxel and may be exacerbated by its combination with vinorelbine. Study of hospital-based patients treated with taxane-based chemotherapy is underway to find out the frequency of such complications.

DDE and DDT in breast adipose tissue and risk of female breast cancer.

A case-control study was conducted in Connecticut from 1994 to 1997 to investigate the relation between dichlorodiphenyldichloroethane (DDE) and dichlorodiphenyltrichloroethane (DDT) exposure and breast cancer risk. Cases and controls were women aged 40-79 years, who had breast-related surgery at the Yale-New Haven Hospital and from whose surgical specimen the authors could obtain at least 0.4 g of breast adipose tissue for chemical analyses. A total of 304 incident breast cancer cases (including 62 in situ carcinomas) and 186 benign breast disease controls were recruited into the study. Tissue levels of DDE and DDT were measured using gas chromatography. Statistical significance for comparisons of mean levels of DDE and DDT was calculated using analysis of variance and rank sum tests. A logistic regression model was used to estimate the association and to control confounding. The age-adjusted geometric mean tissue level of DDE for cases (736.5 ppb) was similar to that for the controls (784.1 ppb). DDT levels were also similar for cases (51.8 ppb) and controls (55.6 ppb). The adjusted odds ratio is 0.9 (95% confidence interval: 0.5, 1.5) for DDE and 0.8 (95% confidence interval: 0.5, 1.5) for DDT when the highest quartile was compared with the lowest. These results do not support an association between adipose tissue levels of DDE and DDT and breast cancer risk.

Hepatocellular carcinoma and intrahepatic peripheral cholangiocarcinoma: enhancement patterns with quadruple phase helical CT--a comparative study.

PURPOSE: To define the hemodynamic features of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma by using quadruple phase helical computed tomography (CT) and determine the value of this information in characterizing tumors. MATERIALS AND METHODS: Helical CT of the liver was performed in 45 patients with newly diagnosed HCC or peripheral cholangiocarcinoma. Scans were obtained before and 25 seconds, 70 seconds, and 2-6 minutes after the start of the contrast material injection. The intensity and spatial distribution of contrast material uptake were evaluated during all phases. Time-attenuation curves were established for each lesion. Relative attenuation and lesion conspicuity were assessed. A diagnostic confidence level was assigned to each lesion. RESULTS: In the majority of HCC lesions, a single, early peak of enhancement followed by a continuous decrease in tumor attenuation over time was seen. The greatest tumor conspicuity occurred during the delayed phase. In cholangiocarcinoma, tumor attenuation increased during the delayed phase. In the majority of lesions, the greatest tumor conspicuity was seen during the portal venous phase. In both tumor types, the diagnostic confidence level improved when the delayed phase was used. CONCLUSION: The variation over time in the intensity of contrast enhancement in HCC and cholangiocarcinoma differs sufficiently to make this a useful diagnostic criterion. The delayed phase is particularly important because it amplifies this difference.

Prognostic implications of response to preoperative infusional chemoradiation in locally advanced rectal cancer.

BACKGROUND AND PURPOSE: To evaluate the influence of response to preoperative infusional chemoradiation on outcome parameters among patients with locally advanced rectal cancer. MATERIALS AND METHODS: Preoperative chemoradiotherapy, 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m2 per day), was given to 117 patients. As determined by pretreatment endorectal ultrasound (EUS), 96% of cases were Stage T3, and 51% had EUS evidence of perirectal adenopathy. Surgery was performed approximately 6 weeks after chemoradiation therapy. Postoperatively adjuvant systemic therapy, consisting of 400-425 mg/m2 of 5-fluorouracil plus 20 mg/m2 leucovorin for 5 days, was administered every 28 days for six cycles. Outcome parameters of local control (LC), freedom from distant metastases (DMC), disease-free survival (DFS) and cancer specific survival (CSS) were evaluated relative to primary tumor characteristics. RESULTS: The final post-treatment pathological tumor stages were complete response in 27%, Tis-2 N0 in 26%, T2 N1 in 5%, T3 N0 in 21%, T3 N1 in 15%, T4 N0 in 5% and T4 N1 in 1%. Down-staging occurred in 61% of cases. The pretreatment primary tumor size only influenced rates of local control (P < 0.03) and had no other influence on outcome parameters. Pretreatment evidence of perirectal lymph node involvement had no impact on outcome parameters. Pathologic evidence of nodal involvement did affect DMC (P < 0.002) and DFS (P < 0.003). Pathologic evidence of response did influence freedom from the development of distant metastases (P < 0.004). On pairwise analysis this relationship held only when responders were compared to non-responders. No difference was observed based on the level of downstaging at the primary tumor. Correspondingly, DFS was improved when non-responders were compared to downstaged patients (P < 0.01). Response to preoperative chemoradiation failed to affect rates of LC or CSS. For the group as a whole, adjuvant chemotherapy improved only CSS (P < 0.03). Adjuvant chemotherapy was given to 74 patients, 36 of whom had responded to preoperative chemoradiation. Improvements were only seen in DFS (P < 0.03) when down-staged patients were compared to the non-responders who received adjuvant chemotherapy. In addition, the DFS rates were lower in the non-responder group who received adjuvant chemotherapy even when they were compared to down-staged patients who did not receive adjuvant chemotherapy (P < 0.04). CONCLUSION: Consistent with other reports, disease free survival and subsequent development of distant metastases is reduced in the more than 60% of patients who respond to preoperative infusional chemoradiation. Evidence of response appears more significant than the degree of response. At present, no impact is seen on cancer specific survival rates. Consideration should be given for strategies that base selection of subsequent adjuvant chemotherapy on response to preoperative chemoradiation.

Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience.

PURPOSE: To evaluate the rates of tumor downstaging after preoperative chemoradiation for locally advanced rectal cancer. MATERIALS AND METHODS: Preoperative chemoradiotherapy (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m2/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/XRT, surgery was performed. RESULTS: The pathological tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4NI in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor downstaging occurred in 72 (62%) cases. Only 3% of cases had pathologic evidence of progressive disease. Pretreatment tumor size (< 5 cm vs. > or = 5 cm) was the only factor predictive of tumor downstaging (p < 0.04). A decrease of > 1 T-stage level was accomplished in 45% of those downstaged. Overall, a sphincter-saving (SP) procedure was possible in 59% of patients and an abdominoperineal resection (APR) was required in 41 % of cases. Factors predictive of SP included downstaging (p < 0.03), age > 40 years (p < 0.007), pretreatment tumor distance, 3 to 6 cm from the anal verge (p < 0.00001), tumor size <6 cm (p < 0.02), mobility (p < 0.004), tumor stage 6 cm from the anal verge, SP was performed in 14 of the 15 (93%) patients with a CR and 32 of 33 (97%) of patients with residual disease (p < 0.00004). CONCLUSIONS: Significant tumor downstaging results from preoperative chemoradiation allowing sphincter sparing surgery in over 40% of patients whose tumors were located < 6 cm from the anal verge and who otherwise would have required colostomy.

Metastases to the pancreas from renal cell carcinoma: findings on three-phase contrast-enhanced helical CT.

OBJECTIVE: Our goal was to define the lesion enhancement characteristics of renal cell carcinoma metastases to the pancreas using three-phase helical CT. MATERIALS AND METHODS: Thin-section three-phase contrast-enhanced CT scans of nine patients with renal cell carcinoma metastases to the pancreas were evaluated. The helical CT protocol included 3-mm collimation and a 2:1 pitch. Scans through the pancreas were obtained in three series beginning 25, 60, and 120 sec after the start of administration of i.v. contrast material delivered at 3 ml/sec. The Hounsfield densities of the pancreatic lesions and normal pancreatic parenchyma during each of the enhancement phases were recorded and compared. RESULTS: The enhancement patterns of the metastatic deposits and the normal pancreas differed. Thirty-four lesions ranging in size from 6 to 110 mm were identified. All metastases showed rapid enhancement during the early (arterial and portal) phases, resulting in differential attenuations (compared with normal pancreatic parenchyma) of approximately 50-100 H. The differential attenuations were approximately 5-45 H on delayed-phase scans, resulting in poorer conspicuity of the lesions. Multifocal metastases were clearly identified on the early-phase scans in seven patients. CONCLUSION: Renal cell carcinoma metastases to the pancreas enhance most conspicuously during the early phases of helical CT. Such metastases may fail to be appreciated in the delayed phase. In patients with suspected renal cell carcinoma metastases to the pancreas, early-phase scanning after i.v. contrast administration should be performed.