Showing papers in "Cancer in 2001"

Cancer risk in patients with inflammatory bowel disease: a population-based study.

Abstract: BACKGROUND The objective of the current study was to determine the incidence of cancer among persons with inflammatory bowel disease (IBD) and to compare these incidence rates with those of the non-IBD population using population-based data from the administrative claims data of Manitoba's universal provincial insurance plan (Manitoba Health). METHODS IBD patients were matched 1:10 to randomly selected members of the population without IBD based on year, age, gender, and postal area of residence. The incidence of cancer was determined by linking records from the IBD and non-IBD cohorts with the comprehensive Cancer Care Manitoba registry. Incidence rates and rate ratios (IRR) were calculated based on person-years of follow-up (Crohn's disease = 21,340 person-years and ulcerative colitis [UC] = 19,665 person-years) for 1984–1997. RESULTS There was an increased IRR of colon carcinoma for both Crohn disease patients (2.64; 95% confidence interval [95% CI], 1.69–4.12) and UC patients (2.75; 95% CI, 1.91–3.97). There was an increased IRR of rectal carcinoma only among patients with UC (1.90; 95% CI, 1.05–3.43) and an increased IRR of carcinoma of the small intestine only in Crohn disease patients (17.4; 95% CI, 4.16–72.9). An increased IRR of extraintestinal tumors was observed only for the liver and biliary tract in both Crohn disease patients (5.22; 95% CI, 0.96–28.5) and UC patients (3.96; 95% CI, 1.05–14.9). There was an increased IRR of lymphoma for males with Crohn disease only (3.63; 95% CI, 1.53–8.62), and this finding did not appear to be related to use of immunomodulatory therapy. Compared with controls, Crohn's disease was associated with an increased risk of cancer overall, but UC was not. CONCLUSIONS There appear to be similar increased risks for developing colon carcinoma and hepatobiliary carcinoma among patients with Crohn disease and UC. There is an increased risk of developing rectal carcinoma in UC patients, an increased risk of developing carcinoma of the small bowel in Crohn disease patients, and an increased risk of developing lymphoma among males with Crohn disease. Cancer 2001;91:854–62. © 2001 American Cancer Society.

Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review.

Abstract: BACKGROUND Anemia is common in cancer patients, although the prevalence is influenced both by the type of malignancy and the choice of treatment. Individual studies have compared the survival of patients with and without anemia and have shown reduced survival times in patients with various malignancies, including carcinoma of the lung, cervix, head and neck, prostate, lymphoma, and multiple myeloma. The objective of this study was to systematically review, to summarize, and to obtain an overall estimate of the effect of anemia on survival in patients with malignant disease. METHODS A comprehensive literature review was carried out using the MEDLINE data base and reviewing the reference lists from published studies. Two hundred papers were identified. Of these, 60 papers that reported the survival of cancer patients according to either hemoglobin levels or the presence of anemia were included. Among these papers, 25% related to patients with lung carcinoma, 17% related to patients with head and neck carcinoma, 12% related to patients with multiple myeloma, 10% related to patients with prostate carcinoma, 8% related to patients with cervicouterine carcinoma, 7% related to patients with leukemia, 5% related to patients with lymphoma, and 16% related to patients with other types of malignancies. RESULTS The relative risk of death increased by 19% (95% confidence interval, 10–29%) in anemic patients with lung carcinoma, by 75% (37–123%) in anemic patients with head and neck carcinoma, by 47% (21–78%) in anemic patients with prostate carcinoma, and by 67% (30–113%) in anemic patients with lymphoma. The overall estimate increase in risk was 65% (54–77%). CONCLUSIONS Anemia is associated with shorter survival times for patients with lung carcinoma, cervicouterine carcinoma, head and neck carcinoma, prostate carcinoma, lymphoma, and multiple myeloma. Cancer 2001;91:2214–21. © 2001 American Cancer Society.

Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis.

Abstract: BACKGROUND To the authors' knowledge, there are no long-term cohort studies of lymphedema, despite the substantial morbidity of arm swelling. The goal of this study was to identify prevalence of breast carcinoma–related lymphedema, time of onset, and associated predictive factors. METHODS A cohort of 923 women consecutively treated with mastectomy and complete axillary dissection at our center between 1976 and 1978 was observed intensively for 20 years. Two hundred sixty-three study subjects (28.5%) who were alive and recurrence free constituted the cohort for the current study. A subset of 52 women (20% of study population) with contralateral mastectomy was analyzed separately. Subjects reported circumferential arm measurements taken using a validated instrument. In addition to providing analysis of clinical and treatment variables, this study is the first to the authors' knowledge to analyze possible etiologic factors in the posttreatment years, such as occupation, general physical activity, and sports/leisure activities. Univariate and multivariate analytic methods were used. RESULTS At 20 years after treatment, 49% (128 of 263) reported the sensation of lymphedema. Arm swelling measurements were severe (≥ 2.0 in [5.08 cm]; patients reported measurement in inches) for 13% (33 of 263 women). Seventy-seven percent (98 of 128) noted onset within 3 years after the operation; the remaining percentage developed arm swelling at a rate of almost 1% per year. Of the 15 potential predictive factors analyzed, only 2 were statistically significantly associated with lymphedema: arm infection/injury and weight gain since operation (P < 0.001 and P = 0.02, respectively). CONCLUSIONS This defined cohort, treated by axillary dissection 20 years ago, documents the high prevalence of lymphedema and its time course. Two significantly associated factors, both potentially controllable, are identified. The current study provides further support for treatments that limit lymph node dissection. The authors are prospectively evaluating patients undergoing sentinel lymph node biopsy. Cancer 2001;92:1368–77. © 2001 American Cancer Society.

Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group.

Abstract: BACKGROUND Histologic grade is said to be the most important prognostic factor in adult soft tissue sarcomas (STS), but most grading systems have been tested in the overall sarcoma group and the predictive value of histologic grade needs to be assessed specifically for each of the histologic categories. METHODS From 1980 to 1994, 1240 nonmetastatic patients were entered in the French STS database. The following parameters were studied: patient's age and gender, previous history, tumor location, size and depth, neurovascular or bone involvement (NBI), histologic type and subtype, and grade (the French Federation of Cancer Centers [FNCLCC] system). Median follow-up for the survivors was 88 months; only 5% of patients were lost to follow-up. The authors performed univariate and multivariate analyses for metastasis-free survival for the overall sarcoma group and for every main histologic type. RESULTS In order of importance, parameters were respectively retained as independent predictors of metastasis as follows: grade, tumor size, NBI and tumor depth for the overall group, grade and NBI for malignant fibrous histiocytomas (n = 349), tumor size, histologic subtype and grade for liposarcomas (n = 188), NBI, grade and tumor size for leiomyosarcomas (n = 148), grade and NBI for synovial sarcomas (n = 125), grade for unclassified sarcomas (n = 140), and sarcomas of other types (n = 158). No parameter was significant for malignant schwannomas (n = 72) or for rhabdomyosarcomas (n = 60). CONCLUSION In this study, histologic grade appeared as an independent predictor of metastasis development in the main histologic types of adult STS, with the exception of malignant schwannomas and rhabdomyosarcomas. Cancer 2001;91:1914–26. © 2001 American Cancer Society.

Anastrozole Is Superior to Tamoxifen as First-Line Therapy in Hormone Receptor Positive Advanced Breast Carcinoma Results of Two Randomized Trials Designed for Combined Analysis

Abstract: BACKGROUND Two randomized, double-blind trials have compared tamoxifen 20 mg daily and the selective, nonsteroidal aromatase inhibitor anastrozole 1 mg daily as first-line therapy for advanced breast carcinoma (ABC) in postmenopausal women. The trials were prospectively designed to allow for combined data analyses. METHODS The combined study population included 1021 postmenopausal women (median age, 67 years [range, 30–92]) with ABC whose tumors were either estrogen and/or progesterone receptor positive or of unknown receptor status. Primary endpoints were time to progression (TTP), objective response, and tolerability. RESULTS At a median duration of follow-up of 18.2 months, anastrozole was at least equivalent to tamoxifen in terms of median TTP (8.5 and 7.0 months, respectively; estimated hazard ratio [tamoxifen relative to anastrozole], 1.13 [lower 95% confidence level, 1.00]). In a retrospective subgroup analysis, anastrozole was superior to tamoxifen with respect to TTP (median values of 10.7 and 6.4 months for anastrozole and tamoxifen, respectively, two-sided P = 0.022) in patients with estrogen and/or progesterone receptor positive tumors (60% of combined trial population). In terms of objective response, 29.0% of anastrozole and 27.1% of tamoxifen patients achieved either a complete response (CR) or a partial response (PR). Clinical benefit (CR + PR + stabilization of ≥ 24 weeks) rates were 57.1% and 52.0% for anastrozole and tamoxifen, respectively. Both anastrozole and tamoxifen were well tolerated. Anastrozole led to significantly fewer venous thromboembolic (P = 0.043; not adjusted for multiple comparisons) events, and vaginal bleeding was reported in fewer patients treated with anastrozole than with tamoxifen. CONCLUSIONS In postmenopausal women with hormonally sensitive ABC, anastrozole should be considered as the new standard first-line treatment. Cancer 2001;92:2247–58. © 2001 American Cancer Society.

Early lung cancer action project: initial findings on repeat screenings.

Abstract: Background The Early Lung Cancer Action Project (ELCAP) was designed to evaluate the usefulness of annual computed tomography (CT) screening for lung carcinoma. With the baseline results having been reported previously, the focus of the current study was on the early results of the repeat screenings. Methods A cohort of 1000 high-risk individuals was recruited for baseline and annual repeat CT screening. At last follow-up, a total of 1184 annual repeat screenings had been performed. A positive result from the screening test was defined as newly detected, one to six noncalcified pulmonary nodules with interim growth. The diagnostic workup of the individuals was guided by recommendations supplied by the ELCAP investigators to the collaborating clinicians. Results Of the 1184 repeat CT screenings, the test result was positive in 30 (2.5%). In 2 of these 30 cases, the individual died (of an unrelated cause) before diagnostic workup and the nodule(s) resolved in another 12 individuals. In the remaining 16 individuals, the absence of further growth was documented by repeat CT in 8 individuals and further growth was documented in the remaining 8 individuals. All eight individuals with further nodular growth underwent biopsy and malignancy was diagnosed in seven. Six of these seven malignancies were nonsmall cell carcinomas (five of which were Stage IA and one of which was Stage IIIA) and the one small cell carcinoma was found to be of limited stage. The median size dimension of these malignancies was 8 mm. In another two subjects, symptoms prompted the interim diagnosis of lung carcinoma. Neither of these malignancies was nodule-associated but rather were endobronchial; one was a Stage IIB nonsmall cell carcinoma and the other was a small cell carcinoma of limited stage. Conclusions False-positive screening test results are uncommon and usually manageable without biopsy; compared with no screening, such screenings permit diagnosis at substantially earlier and thus more curable stages. Annual repetition of CT screening is sufficient to minimize symptom-prompted interim diagnoses of nodule-associated malignancies.

Beyond randomized controlled trials: organized mammographic screening substantially reduces breast carcinoma mortality.

Abstract: BACKGROUND, The efficacy of mammographic screening in the reduction of breast carcinoma mortality has been demonstrated in randomized controlled trials. However, the evaluation of organized screeni ...

Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases: A double-blind, randomized dose-response study

Abstract: BACKGROUND This study evaluated the dose–response relation for zoledronic acid, a new generation high potency bisphosphonate, given as a 5-minute infusion in patients with malignant osteolytic disease. METHODS Two-hundred eighty patients with osteolytic lesions due to metastatic breast carcinoma or multiple myeloma were randomized to double-blind treatment with either 0.4, 2.0, or 4.0 mg of zoledronic acid or 90 mg pamidronate. The primary efficacy endpoint was the proportion of patients receiving radiation to bone. Other skeletal-related events, bone mineral density (BMD), bone markers, Eastern Cooperative Oncology Group performance status, pain and analgesic scores, and safety also were evaluated. RESULTS Zoledronic acid at doses of 2.0 and 4.0 mg and pamidronate at a dose of 90 mg each significantly reduced the need for radiation therapy to bone (P < 0.05) in contrast with 0.4 mg zoledronic acid, which did not. Skeletal-related events of any kind, pathologic fractures, and hypercalcemia also occurred less frequently in patients treated with 2.0 or 4.0 mg zoledronic acid or pamidronate than with 0.4 mg zoledronic acid. Increases in lumbar spine BMD (6.2–9.6%) and decreases in the bone resorption marker N-telopeptide (range, −37.1 to −60.8%) were observed for all treatment groups. Skeletal pain, fatigue, nausea, vomiting, and headache were the most commonly reported adverse events. Adverse events were similar in nature and frequency with zoledronic acid and pamidronate. CONCLUSIONS A 5-minute infusion of 2.0–4.0 mg zoledronic acid was at least as effective as a 2-hour 90-mg pamidronate infusion in treatment of osteolytic metastases. A 0.4-mg dose of zoledronic acid was significantly less effective. Both zoledronic acid and pamidronate were well tolerated. Cancer 2001;91:1191–200. © 2001 American Cancer Society.

Nasal and paranasal sinus carcinoma: are we making progress? A series of 220 patients and a systematic review.

Abstract: The authors reviewed treatment results in patients with nasal and paranasal sinus carcinoma from a large retrospective cohort and conducted a systematic literature review.

Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma.

Abstract: BACKGROUND Cells with deficient DNA mismatch repair develop microsatellite instability. Extensive microsatellite instability (MSI-high) is characteristic of colorectal carcinomas in hereditary nonpolyposis colorectal carcinoma (HNPCC) and in 10–% 15% of sporadic colorectal carcinomas. Microsatellite instability-high colorectal carcinomas differ from others in important clinical and pathologic features. However, MSI typing is expensive and not widely available. Microsatellite instability type may be predicted by tumor-infiltrating lymphocytes (TILs), which can be evaluated with ordinary light microscopy. METHODS The authors evaluated TILs as a pathology screen for MSI-high status in 138 colorectal carcinomas that had been evaluated for MSI in a variety of studies. This case series was systematically enriched with HNPCC and other MSI-high cases to allow accurate sensitivity and specificity estimation. Tumor-infiltrating lymphocytes were quantitated as TILs per 10 high-power microscopic fields by an observer blinded to MSI status. RESULTS Of the 138 carcinomas studied, 67 (48.6%) were MSI-high, 22 (15.9%) were MSI-low, and 49 (35.5%) were MSI-stable. All 25 HNPCC colorectal carcinomas were MSI-high. Tumor-infiltrating lymphocytes counts ranged from 0 to 300, with a markedly skewed distribution (median, 11; mean, 36). Sensitivity and specificity for selected cut points of TIL count were computed. Using a TIL count of 5 as a cut point yields a sensitivity of 93% and specificity of 62%. In a population in which 12% were MSI-high, consideration of TIL could reduce the number of colorectal carcinomas referred for MSI testing by greater than one-half, and still 93% of the MSI-high carcinomas would be identified. CONCLUSIONS The presence of MSI defines a subset of colorectal carcinomas with special molecular etiology and characteristic clinical, pathologic features, inclusive of increased survival. The authors conclude that quantification of TILs may provide a simple, single criterion for choosing which colorectal carcinomas are candidates for MSI testing. Cancer 2001;91:2417–22. © 2001 American Cancer Society.

Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma.

Abstract: BACKGROUND Epidemiologic evidence points to a connection between viral infection by the human papillomavirus (HPV) and a subgroup of squamous cell carcinoma of the oropharynx. To assess the impact of HPV infection on the response of these tumors toward radiotherapy, the authors retrospectively determined the presence of the virus and the integrity of the viral E2 gene in tumors of patients who have undergone curative irradiation. METHODS Paraffin embedded biopsies from 99 patients were analyzed for HPV infection and E2 gene integrity by multiplex PCR. The experimental findings were correlated with clinical characteristics, known risk factors, and treatment outcome. RESULTS Fourteen of 99 tumors were HPV positive (11 HPV16, 1 HPV33, 1 HPV35, and 1 HPV45). Human papillomavirus positivity was closely linked to female gender (odds ratio [OR], 5.75; P = 0.004), age older than 56 years (OR, 7.42; P = 0.012), nonsmokers (OR, 21.33; P = 0.00001), and alcohol abstainers (OR, 5.35; P = 0.012). There was an inverse association with p53 nuclear immunoreactivity (OR, 0.06; P = 0.008). The Kaplan–Meier survival estimates showed a better local control (P = 0.050, log-rank) and a better overall survival (P = 0.046, log-rank) for patients with HPV positive tumors. In the multivariate analysis, HPV positivity remained to be associated with a lower risk of local failure (risk ratio [RR], 0.31; P = 0.048). Four of 11 HPV16 positive tumors had a disrupted E2 gene. Only tumors with a disrupted E2 gene manifested local treatment failure. CONCLUSIONS Human papillomavirus positivity designates a specific subgroup of oropharyngeal squamous cell carcinomas of the oropharynx that arise preferentially among individuals with no consumption of tobacco and alcohol and that have a favorable outcome attributable to an increased sensitivity toward radiotherapy. Cancer 2001;92:805–13. © 2001 American Cancer Society.

Demographic variations in the rising incidence of esophageal adenocarcinoma in white males.

Abstract: BACKGROUND The rise in adenocarcinoma (AC) of the esophagus has been reported in several papers. However, the results are only comparable to a limited extent, because they are based on differing periods and different computational methods. The purpose of the current investigation was to collect the available data and to analyze them in a unified manner. METHODS The authors requested data on the incidence of AC of the esophagus for each year since 1960 from 43 tumor registries in North America, Europe, and Australia. The data from 22 centers were used. The trend was calculated by fitting the data to an exponential growth model. RESULTS The incidence of AC of the esophagus in white males is rising in most countries. The highest values of the estimated incidence rate in the year 2000 were found in Great Britain (5.0– 8.7 cases per 100,000 population) and in Australia (4.8 cases per 100,000 population) followed by The Netherlands (4.4 cases per 100,000 population), the United States (3.7 cases per 100,000 population), and Denmark (2.8 cases per 100,000 population). Low rates (< 1.0 cases per 100,000 population) were found in Eastern Europe. The largest changes in incidence were reported in the Southern European countries, with an estimate of the average increase over six registries of 30% per year; in Australia, with an average increase of 23.5% per year; and in the United States, with an average increase of 20.6% per year. The rates of increase ranged from 8.7% to 17.5% on average in Northern Europe, Central Europe, and the United Kingdom. In Eastern Europe, at most, there was a minor rise in incidence. CONCLUSIONS In the Western industrialized nations, the analyzed data show that the incidence of AC of the esophagus has been rising rapidly in the last 20 years. The only exceptions to date are the countries of Eastern Europe. Cancer 2001;92:549–55. © 2001 American Cancer Society.

Curative treatment of peritoneal carcinomatosis arising from colorectal cancer by complete resection and intraperitoneal chemotherapy.

Abstract: BACKGROUND Peritoneal carcinomatosis (PC) is fatal, despite standard systemic chemotherapy. A new approach that combines maximal surgery with maximal regional chemotherapy has potential to cure selected patients who have colorectal PC. The authors have reported the oncologic results of this combined treatment. METHODS The authors performed a retrospective study of 64 patients who had PC arising from colorectal adenocarcinomas, 19 (29.6%) of whom also had other metastases. These patients were treated by complete resection of all detectable tumors and by a 5-day course of early intraperitoneal chemotherapy (EPIC) with mitomycin C, then by 5-fluorouracil (n = 37), or by intraoperative intraperitoneal chemohyperthermia (IPCH) with mitomycin C, alone or combined with cisplatin (n = 27), in 2 separate trials. In the trial of IPCH, aimed at selecting the most reliable procedure in terms of spatial diffusion and thermal homogeneity, the 27 patients were treated with 7 different procedures. The extent of PC was assessed precisely by using a peritoneal index. The median follow-up period for the entire patient population was 51.7 months. RESULTS The postoperative mortality and morbidity rates were 9.3% and 54.6%, respectively. Most severe complications occurred in patients who required extensive cytoreductive surgery. Global and disease-free survival rates were respectively 60.1% and 54.7% at 2 years and were 27.4% and 18.4% at 5 years. Results were significantly better (P = 0.04) when patients were metastasis-free (apart from PC) and when the peritoneal index was lower than 16 (P = 0.005). IPCH seemed to be more effective than EPIC for treatment of PC. CONCLUSION This treatment plan, which combined maximal surgery with maximal regional chemotherapy, cured approximately 25% of patients. This strategy was mainly applicable to patients with limited intraperitoneal cancer volume and no extraperitoneal involvement. IPCH proved to be more effective than EPIC but more difficult to use correctly. Future results should improve through routine use of the optimal hyperthermia procedure, with improvements in the composition of instillate, better patient selection, and the reduction in the rate of complications that occurs with physician experience. Cancer 2001;92:71–6. © 2001 American Cancer Society.

Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung.

Abstract: BACKGROUND. The majority of lung carcinoma cases occur in current or former smokers. K-ras gene mutations are common in lung adenocarcinoma and have been associated with cigarette smoking, asbestos exposure, and female gender. METHODS. In the current study, the authors examined the contribution of cigarette smoking to K-ras gene mutations in patients with primary lung adenocarcinoma. Smoking histories were obtained from 106 prospectively enrolled patients with primary adenocarcinoma of the lung. RESULTS. K-ras mutations were detected in the primary tumor using an allele-specific ligation assay. Ninety-two of the 106 patients (87%) with lung adenocarcinoma were smokers. Nonsmokers with this tumor were more likely to be women (11 of 14; 79%), whereas the majority of smokers (57%) were men. K-ras mutations were detected in 40 of 106 tumors (38%) and were significantly more common in smokers compared with nonsmokers (43% vs. 0%; P = 0.001). CONCLUSIONS. The results of the current study confirm and extend previous observations that smokers with adenocarcinoma of the lung are more likely to have K-ras mutant tumors compared with nonsmokers. The strong link between cigarette smoking and K-ras mutations in adenocarcinoma of the lung supports the role of specific tobacco carcinogens in the etiology of this malignancy.

Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone.

Abstract: BACKGROUND Surgery is the standard treatment for patients with resectable esophageal carcinoma, but the long term prognosis of these patients is unsatisfactory. Some randomized trials of preoperative chemotherapy suggest that the prognosis of patients who respond may be improved. METHODS This randomized, controlled trial compared patients with clinically resectable esophageal epidermoid carcinoma who underwent surgery alone (Arm A) with those who received preoperative chemotherapy (Arm B). Overall survival and the prognostic impact of major response to chemotherapy were analyzed. Forty-eight patients were enrolled in each arm. Chemotherapy consisted of two or three cycles of cisplatin (100 mg/m2 on Day 1) and 5- fluorouracil (1000 mg/m2 per day continuous infusion on Days 1–5). In both study arms, transthoracic esophagectomy plus two-field lymphadenectomy was performed. The two groups were comparable in terms of patient characteristics. RESULTS Forty-seven patients were evaluable in each arm. The curative resection rate was 74.4% (35 of 47 patients) in Arm A and 78.7% (37 of 47 patients) in Arm B. Treatment-related mortality was 4.2% in both arms. The response rate to preoperative chemotherapy was 40% (19 of 47 patients), including 6 patients (12.8%) who achieved a pathologic complete responses. Overall survival was not improved significantly. The 19 patients in Arm B who responded to chemotherapy and underwent curative resection had significantly better 3-year and 5-year survival rates (74% and 60%, respectively) compared with both nonresponders (24% and 12%, respectively; P = 0.0002) and patients in Arm A who underwent complete resection (46% and 26%, respectively; P = 0.01): Patients who achieved a pathologic complete response (P = 0.01), but not those who achieved a partial response (P = 0.2), had significantly improved survival. CONCLUSIONS Patients with resectable esophageal carcinoma who underwent preoperative chemotherapy and obtained a pathologic complete response had a significantly improved long term survival. Major efforts should be undertaken to identify patients before neoadjuvant treatments who are likely to respond. Cancer 2001;91:2165–74. © 2001 American Cancer Society.

Multicenter, Phase II study of capecitabine in taxane-pretreated metastatic breast carcinoma patients

Abstract: BACKGROUND Capecitabine is an oral, tumor-targeted fluoropyrimidine carbamate with high activity in metastatic breast carcinoma and in paclitaxel-pretreated metastatic breast carcinoma. METHODS The current multicenter, Phase II trial assessed the efficacy and safety of intermittent oral capecitabine, 1255 mg/m2 twice daily (2 weeks of treatment followed by a 1-week rest period), in patients with metastatic breast carcinoma in whom prior taxane therapy had failed. All patients had failed treatment or had disease that was refractory to two or three previous chemotherapy regimens, one of which contained a taxane. Nearly all patients (96%) also had received prior anthracycline chemotherapy. Seventy-five patients were recruited at 5 centers, 74 of whom received treatment. RESULTS The overall response rate was 26%, with response rates of 27% and 20%, respectively, in the subgroups of patients previously pretreated with paclitaxel (n = 47) or docetaxel (n = 27). The median survival was 12.2 months, the median duration of response was 8.3 months, and the median time to disease progression was 3.2 months. The most common treatment-related adverse events (all grades) were hand-foot syndrome (62%), diarrhea (58%), nausea (55%), emesis (37%), and stomatitis (34%). However, the majority were mild to moderate in intensity and only three patients experienced Grade 4 (according to the National Cancer Institute of Canada Common Toxicity criteria) adverse events. The only Grade 3 treatment-related adverse events reported in ≥ 10% of the patients were hand-foot syndrome (22%), diarrhea (16%), and stomatitis (12%). Myelosuppression and alopecia were rare, and there were no reported treatment-related deaths. CONCLUSIONS The results of the current study demonstrate that capecitabine is an effective and well tolerated treatment in patients with taxane-refractory or taxane-failing metastatic breast carcinoma. In addition, it is a convenient, orally administered drug, which makes it an attractive agent for use in outpatient treatment. Cancer 2001;92:1759–68. © 2001 American Cancer Society.

Prognostic factors in retroperitoneal sarcoma: a multivariate analysis of a series of 165 patients of the French Cancer Center Federation Sarcoma Group.

Abstract: BACKGROUND. Surgery is the main prognostic factor in retroperitoneal sarcoma. However, despite progress, surgery alone is rarely curative, and analysis of the causes of failures and of other prognostic factors are warranted to ascertain treatment orientations. METHODS. Data of patients treated from 1.80 to 12.94 for primary retroperitoneal sarcoma were extracted from the French Federation of Cancer Centers Sarcoma Group registry. Univariate and multivariate analysis were performed for initial local control and for local and general outcome. One hundred sixty-five patients (median age, 54 years; range, 16-82 years) were identified. Median tumor size was 15 cm (range, 2-70 cm); 31% of tumors presented with neurovascular or bone involvement. Liposarcoma, leiomyosarcoma, and malignant fibrous histiocytoma represented 66% of the tumors. Eighty-four percent of the tumors were of high or intermediate grade. Twenty patients had initial metastases. Multimodality treatment included surgery (150 patients), radiotherapy (92 patients), and chemotherapy (77 patients). Complete excision was achieved in 94 of 145 nonmetastatic patients. Median follow-up was 47 months (range, 3-160 months). RESULTS. Actuarial overall 5-year survival rate (median) was 46% (51 months). The main prognostic factors for survival were initial metastases and surgery, which represented the major treatment-linked factor. High-grade of tumors affected local recurrence, metastatic recurrence, and survival. Adjuvant radiotherapy was significantly associated with reduced local recurrence. Various evolutive patterns were observed with histologic subtypes. CONCLUSIONS. Aggressive surgery remains mandatory in retroperitoneal sarcoma, but a randomized trial is needed to evaluate the place of radiotherapy for local control.

Artificial neural networks: opening the black box.

Abstract: Artificial neural networks now are used in many fields They have become well established as viable, multipurpose, robust computational methodologies with solid theoretic support and with strong potential to be effective in any discipline, especially medicine For example, neural networks can extract new medical information from raw data, build computer models that are useful for medical decision-making, and aid in the distribution of medical expertise Because many important neural network applications currently are emerging, the authors have prepared this article to bring a clearer understanding of these biologically inspired computing paradigms to anyone interested in exploring their use in medicine They discuss the historical development of neural networks and provide the basic operational mathematics for the popular multilayered perceptron The authors also describe good training, validation, and testing techniques, and discuss measurements of performance and reliability, including the use of bootstrap methods to obtain confidence intervals Because it is possible to predict outcomes for individual patients with a neural network, the authors discuss the paradigm shift that is taking place from previous "bin-model" approaches, in which patient outcome and management is assumed from the statistical groups in which the patient fits The authors explain that with neural networks it is possible to mediate predictions for individual patients with prevalence and misclassification cost considerations using receiver operating characteristic methodology The authors illustrate their findings with examples that include prostate carcinoma detection, coronary heart disease risk prediction, and medication dosing The authors identify and discuss obstacles to success, including the need for expanded databases and the need to establish multidisciplinary teams The authors believe that these obstacles can be overcome and that neural networks have a very important role in future medical decision support and the patient management systems employed in routine medical practice

Epidermal growth factor receptor immunohistochemical reactivity in patients with American Joint Committee on Cancer Stage IV colon adenocarcinoma: implications for a standardized scoring system.

Abstract: BACKGROUND An epidermal growth factor receptor (EGFR) immunohistochemical detection system currently is being developed. The current study attempts to address background EGFR reactivity issues before determining the optimum EGFR scoring system. METHODS Tissue sections from 102 patients with T3N1-2M1 colon adenocarcinoma were stained with a prototype EGFR detection system. The number of cases, location, percentage, and intensity of reactive cells (0+ [none] to 3+ [strong]) were scored and compared with the length of survival. RESULTS Approximately 75.5% of the adenocarcinoma cases had EGFR reactivity; 31.4% of the tumors had 3+ reactivity in 10–50% of the neoplastic cells and 3.9% had 3+ reactivity in > 50% of cells. Increased numbers of reactive cells per case predominantly resulted from increased 3+ reactivity. The mean percentage of 2+ (moderate) and 3+ reactive cells per case increased in the regions of deepest invasion. The mean percentage of 3+ reactivity per case was significantly greater in the deepest tumor region compared with the superficial region (16.9% vs. 7.9%; P = 0.004). EGFR reactivity in metastases appeared to have the strongest correlation with reactivity in the deep regions of colon adenocarcinoma. An increasing percentage of 2+ and 3+ or 3+ only reactivity in the deep region was found to have the strongest correlation with decreased survival (P = 0.0252). CONCLUSIONS EGFR reactivity of 2+ and 3+ may provide a framework for a scoring system. It may be important to evaluate EGFR reactivity in the deepest region of tumor invasion because this region appears to contain the largest percentage of 3+ reactive cells and appears to have the strongest correlation with survival length and EGFR reactivity in lymph node and liver metastases. Cancer 2001;92:1331–46. © 2001 American Cancer Society.

Patients with pseudomyxoma peritonei associated with disseminated peritoneal adenomucinosis have a significantly more favorable prognosis than patients with peritoneal mucinous carcinomatosis.

Abstract: BACKGROUND Pseudomyxoma peritonei (PMP) is a poorly understood condition characterized by disseminated intraperitoneal mucinous tumors, often with mucinous ascites. The term PMP has been applied historically as a pathologic diagnostic term to both benign and malignant mucinous neoplasms that produce abundant extracellular mucin, resulting in a variable and poorly predictable prognosis. A recent study reported a pathologic classification that separated patients into prognostically distinct groups, but the follow-up was relatively short. METHODS Long-term follow-up data were analyzed for a previously reported series of 109 patients with PMP to examine the prognostic utility of a pathologic classification system that divided patients into three groups: disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and peritoneal mucinous carcinomatosis with intermediate or discordant features (PMCA-I/D). Patients whose tumors were classified 25 DPAM (n = 65 patients) had disease that was characterized by histologically bland to low-grade adenomatous mucinous epithelium associated with abundant extracellular mucin and fibrosis, often with an identifiable appendiceal mucinous adenoma that was the source of the peritoneal lesions. Patients whose tumors were classified 25 PMCA (n = 30 patients) had disease that was characterized by peritoneal lesions that displayed the cytologic and architectural features of mucinous carcinoma associated with extracellular mucin, often with an identifiable invasive mucinous adenocarcinoma of the gastrointestinal tract. Patients whose tumors were classified 25 PMCA-I (n = 11 patients) had peritoneal lesions that combined the features of DPAM and PMCA derived from well differentiated mucinous adenocarcinomas associated with adenomas. Patients whose tumors were classified 25 PMCA-D (n = 3 patients) had markedly atypical appendiceal adenomas associated with peritoneal lesions similar to PMCA. RESULTS Patients with DPAM had 5-year and 10-year survival rates of 75% and 68%, respectively (mean follow-up, 96 months; median follow-up, 104 months). Patients with PMCA and PMCA-I/D had a significantly worse prognosis, with 5-year and 10-year survival rates, respectively, of 50% and 21% for PMCA-I/D (mean follow-up, 58 months; median follow-up, 51 months) and 14% and 3% for PMCA (mean follow-up, 27 months; median follow-up, 16 months; P = 0.0001). CONCLUSIONS The term PMP should be used only as a clinical descriptor for patients who have the syndrome of mucinous ascites accompanied by a characteristic distribution of peritoneal mucinous tumors with the pathologic features of DPAM. DPAM should be used as a pathologic diagnostic term for patients with the bland peritoneal mucinous tumors associated with ruptured appendiceal mucinous adenomas and PMP. These patients should not be diagnosed with carcinoma, because they have disease that is distinct pathologically and prognostically from PMCA. Cancer 2001;92:85–91. © 2001 American Cancer Society.

Prevalence, distribution, and viral load of human papillomavirus 16 DNA in tonsillar carcinomas.

Abstract: BACKGROUND Oncogenic human papillomaviruses (HPV) DNA have repeatedly been observed in many head and neck carcinomas (HNSCCs), and HPV infections are currently considered a possible factor in the etiology of these tumors. However, the reported prevalences of HPV-DNA in HNSCC are variable. In the current study the authors used highly sensitive polymerase chain reactions (PCRs) to analyze the occurrence of viral sequences in 98 carefully stratified HNSCCs. The authors determined the load and localization of HPV DNA in a subset of tonsillar carcinomas and their metastases. METHODS Nested PCR and an HPV16 specific single step PCR were used to screen 98 HNSCCs for HPV DNA for genital- and Epidermodysplasia verruciformis (EV)-associated HPVs. Typing was performed by direct sequencing and/or sequencing of cloned amplimers. In two patients HPV16 subtypes in tonsillar carcinomas and their metastases were compared by amplification and sequencing of the long control region of the virus. In a subset of HPV16 positive tonsillar carcinomas and their metastases, localization and viral load were determined using laser assisted microdissection and real time fluorescent PCR, respectively. RESULTS Altogether 25 HNSCCs (26%) were found to be HPV positive. Stratified according to the tumor localization, the frequency of HPV positive lesions was 18% in the oral cavity, 45% for oropharynx, 25% for hypopharynx, 8% for nasopharynx, and 7% for larynx. The highest HPV DNA prevalence (58%) was found in tonsillar carcinomas. The high risk HPV type 16 was found in 84% of positive HNSCCs, in 14% of which EV-associated HPVs were detected. Human papillomavirus sequences were detected in 64% of biopsies with normal mucosa from 11 patients with positive carcinomas. As a control group, 14 tumor free tonsils were analyzed. In none of these specimens were HPV sequences detected. Viral long transcriptional control region sequences in homologous metastases were identical with those in primary tumors and the load values in both locations were roughly comparable. Viral loads differed substantially in different areas of one tumor. Statistical evaluation of data related to clinicopathologic parameters showed a significant linkage of HPV with tonsillar carcinomas compared to other locations. Furthermore, a significant correlation of HPV status of tonsillar carcinomas with tumor grading and alcohol consumption was found. CONCLUSIONS Our study shows a preferential association of HPV-DNA with tonsillar carcinomas. The data support the view of HPV negative and positive tonsillar carcinomas being different tumor entities and conventional cancer risk factors being of less importance in HPV-infected individuals. The HPV genome is located in the cancer cells, whereas the infection of normal mucosa is a rare event. Data on quantification of HPV16 in tonsillar tumors and their metastases showed mean viral loads comparable to other HPV associated malignancies. Cancer 2001;92:2875–84. © 2001 American Cancer Society.

Risk of prostate carcinoma death in patients with lymph node metastasis.

Abstract: BACKGROUND The presence of lymph node metastasis is a poor prognostic sign for patients with prostate carcinoma. Results of published reports on survival among patients with lymph node metastasis are difficult to assess because of treatment selections. The extent to which lymph node status will have an impact on a patient's survival is uncertain. METHODS The authors analyzed 3463 consecutive Mayo Clinic patients who underwent radical prostatectomy and bilateral pelvic lymphadenectomy for prostate carcinoma between 1987 and 1993. Of these patients, 322 had lymph node metastasis at the time of surgery, and 297 lymph node positive patients also received adjuvant hormonal therapy within 90 days of surgery. The progression free rate and the cancer specific survival rate were used as outcome endpoints in univariate and multivariate Cox proportional hazards models. The median follow-up was 6.3 years. Progression was defined by elevation of serum prostate specific antigen (PSA) ≥ 0.4 ng/mL after surgery, development of local recurrence, or distant metastasis documented by biopsy or radiographic examination. RESULTS The 5-year and 10-year progression free survival rates (± standard error [SE]) for patients with lymph node metastasis were 74% ± 2% and 64% ± 3%, respectively, compared with 77% ± 1% and 59% ± 2%, respectively, for patients without lymph node metastasis. The 5-year and 10-year cancer specific survival rates were 94% ± 1% and 83% ± 4%, respectively, compared with 99% ± 0.1% and 97% ± 0.5%, respectively, for patients without lymph node metastasis. Among patients with a single lymph node metastasis, the 5-year and 10-year cancer specific survival rates were 99% ± 1% and 94% ± 3%, respectively. After adjustment for extraprostatic extension, seminal vesicle invasion, Gleason grade, surgical margins, DNA ploidy, preoperative serum PSA concentration, and adjuvant therapy, the hazard ratio for death from prostate carcinoma among patients with a single lymph node metastasis compared with patients who were without lymph node metastasis was 1.5 (95% confidence interval, 0.5–5.0; P = 0.478), whereas the hazard ratio for death from prostate carcinoma was 6.1 (95% confidence interval, 1.9–19.6; P = 0.002) for those with two positive lymph nodes and 4.3 (95% confidence interval, 1.4–13.0; P = 0.009) for those with three or more positive lymph nodes. There was no significant difference in the progression free survival rate among patients with or without lymph node metastasis in multivariate analysis after controlling for all relevant variables, including treatments (hazard ratio,1.0; 95% CI, 0.7–1.3; P = 0.90). CONCLUSIONS Patients with prostate carcinoma who have multiple regional lymph node metastases had increased risk of death from disease, whereas patients with single lymph node involvement appeared to have a more favorable prognosis after radical prostatectomy and immediate adjuvant hormonal therapy. Excellent local disease control was achieved by using combined surgery and adjuvant hormonal therapy in patients with positive lymph nodes. Cancer 2001;91:66–73. © 2001 American Cancer Society.

Incidence trends and risk factors of carcinoid tumors: a nationwide epidemiologic study from Sweden.

Abstract: BACKGROUND: Carcinoids are rare indolent neuroendocrine tumors, mainly located in bowel, stomach, and lung. Their etiology is virtually unknown although a family history is a minor cause.METHODS: Site specific incidence trends and several risk factors of carcinoid tumors were studied based on the nationwide Swedish Family-Cancer Database of 10.2 million individuals and their more than 1 million tumors. Data on a total of 5184 carcinoid tumors were retrieved from the Cancer Registry covering years 1958-1998.RESULTS: The overall age-adjusted incidence rates were 2.0 for men and 2.4/100,000 for women in 1983-1998. Appendix was the main site for women whereas small intestine was the main site for men. The incidence of all carcinoids, including those at the main sites increased during the follow-up period but appeared to plateau in the middle of the 1980s. Appendiceal carcinoids showed an unusually early onset with a maximum incidence at age 15-19 years for women and 20-29 years for men. Among women, parity was not related to the age specific incidence of carcinoid tumors. A Poisson regression analysis showed that family history of carcinoids in first-degree relatives (relative risk, 3.6), well educated social background (relative risk for professionals, 2.8), and birth in large cities were risk factors.CONCLUSIONS: The data suggest that the increase in carcinoid tumors may be largely ascribed to the application of advanced medical viewing techniques that detect asymptomatic tumors. However, the difference in incidence between men and women in appendiceal tumor may be real and independent of parity. (Less)

Effects of exercise on cancer-related fatigue.

Abstract: Cancer patients frequently suffer from fatigue and loss of physical performance. Several biologic, psychologic, and social factors have been suggested as explanations for the origins of fatigue in this context. In most cases, fatigue has a multifactorial genesis. However, recent studies suggest that fatigue may originate from alterations in the muscular energetic systems caused by cancer and its treatment. Furthermore, there is growing evidence that physical exercise programs help prevent the manifestation and reduce the intensity of cancer-related fatigue. In this article, actual evidence of the relationship between fatigue and impairment of physical performance in cancer patients and suggestions for new directions for research are discussed.

Enteral nutrition during the treatment of head and neck carcinoma: is a percutaneous endoscopic gastrostomy tube preferable to a nasogastric tube?

Abstract: BACKGROUND. Multimodality treatments for patients with squamous cell head and neck carcinoma often produce significant mucositis and dysphagia, mandating enteral nutritional support. Patient preference has resulted in the increasing use of percutaneous endoscopic gastrostomy (PEG) tubes rather than nasogastric (NG) tubes. Anecdotal observations of prolonged PEG dependence and of a need for pharyngoesophageal dilatation in PEG patients prompted a retrospective review of the use of both types of feeding tubes. METHODS. Patients who were treated on clinical trials of radiotherapy or chemoradiotherapy for squamous cell head and neck carcinoma between 1989 and 1997 were reviewed retrospectively. Data were gathered regarding demographics, primary tumor site, T and N classifications, and the need for feeding tube placement. In patients requiring feeding tubes, the type and duration of the feeding tube, the need for tracheostomy, the need for pharyngoesophageal dilatation, and the degree of mucositis and dysphagia at baseline and at 1 month, 3 months, 6 months, and 12 months after beginning treatment were recorded. Comparisons were then made between the NG and the PEG groups. RESULTS. Ninety-one feeding tubes were placed in 158 patients over the 8-year interval. A hypopharyngeal primary site, female gender, a T4 primary tumor, and treatment with chemoradiotherapy were predictive of a need for feeding tube placement. NG tubes were placed in 29 patients, and PEG tubes were placed in 62 patients. PEG patients had more dysphagia at 3 months (59% vs. 30%, respectively; P = 0.015) and at 6 months (30% vs. 8%, respectively; P = 0.029) than NG patients. The median tube duration was 28 weeks for PEG patients compared with 8 weeks for NG patients, (P < 0.001). Twenty-three percent of PEG patients needed pharyngoesophageal dilatation compared with 4% of NG patients (P = 0.022). These end points could not be correlated with age, stage, primary tumor site, or tracheostomy placement. CONCLUSIONS. Although patients treated for head and neck carcinoma find that the PEG tube is a more acceptable route for enteral nutrition than the NG tube, in the authors' experience, a PEG tube was required for longer periods of time and was associated with more persistent dysphagia and an increased need for pharyngoesophageal dilatation. A randomized prospective trial is needed to test these observations.

β-catenin mutation and overexpression in hepatocellular carcinoma: Clinicopathologic and prognostic significance

Abstract: BACKGROUND β-Catenin has been recognized as a critical member of the Wnt signaling pathway, and inappropriate activation of this pathway has been implicated in carcinogenesis. METHODS To determine the clinical significance of β-catenin in hepatocellular carcinoma (HCC), we performed mutational analysis at exon 3 of the gene, investigated the subcellular protein expression, and analyzed their clinicopathologic and prognostic significance in 60 patients with resected primary HCC. RESULTS By direct DNA sequencing, somatic mutations of the β-catenin gene were detected in 7 (12%) HCCs. All the mutations were found at the region (exon 3) responsible for phosphorylation and ubiquitination, therefore likely to result in stabilization of free cytoplasmic β-catenin. Nuclear accumulation of the β-catenin protein, similar to the response to the Wnt signal, was found in 10 (17%) HCCs and was closely associated with gene mutation (P < 0.001). In the remaining cases, nonnuclear type overexpression, that is, overexpression in the cytoplasm and/or cytoplasmic membrane, was observed in 31 (62%) HCCs, thus suggesting that the mechanisms leading to β-catenin overexpression may be heterogeneous. HCCs with a nonnuclear type of β-catenin overexpression were more frequently larger than 5 cm in diameter (P = 0.022) and had poorer cellular differentiation (P = 0.037), and the patients had significantly shorter disease-free survival lengths (P = 0.041). Review of the data from previous studies in HCC showed that β-catenin mutations were more frequent in HCV-associated HCC than in HBV-associated ones. CONCLUSIONS β-catenin mutation and deregulation may play an important role in hepatocarcinogenesis. Nonnuclear type β-catenin overexpression appeared to have pathologic and prognostic significance. Cancer 2001;92:136–45. © 2001 American Cancer Society.

Tumor gelatinases and invasion inhibited by the green tea flavanol epigallocatechin-3-gallate.

Abstract: BACKGROUND Given the association of consumption of green tea with prevention of cancer development, metastasis, and angiogenesis, the effect of the main flavanol present, epigallocatechin-3-gallate (EGCG), on two gelatinases most frequently overexpressed in cancer and angiogenesis (MMP-2 and MMP-9) and on tumor cell invasion and chemotaxis were examined. METHODS Zymography, Western blotting, and enzyme linked immuoadsorbent assay were used to analyze the effect of EGCG on MMP-2 and MMP-9 activity, whereas its effect on tumor cell invasion and chemotaxis was examined using modified Boyden chamber assays. RESULTS A Zn2+ chelation-independent, dose-dependent, noncompetitive inhibition by EGCG of both gelatinases was found at concentrations 500 times lower than that reported to inhibit urokinase. Tumor cell invasion of a reconstituted basement membrane matrix, but not chemotaxis, was reduced by 50% with EGCG concentrations equivalent to that in the plasma of moderate green tea drinkers, and 2 orders of magnitude below those of tissue inhibitors of MMPs. Although higher concentrations of EGCG were associated with increased levels of both cell-associated gelatinases and their activator MT1-MMP, no increased gelatinase activation was found, and TIMP-1 and TIMP-2 inhibitors were up-regulated. Finally, concentrations of EGCG active in restraining proliferation and inducing apoptosis of transformed cells were more than 100 times lower than those reported for normal cells. CONCLUSIONS Epigallocatechin-3-gallate is a potent inhibitor of gelatinases and an orally available pharmacologic agent that may confer the antiangiogenic and antimetastatic activity associated with green tea. Cancer 2001;91:822–32. © 2001 American Cancer Society.

Extracapsular spread. A significant predictor of treatment failure in patients with squamous cell carcinoma of the tongue.

Abstract: INTRODUCTION. The presence of nodal metastases remains the most significant predictive factor for regional recurrence and survival in patients treated for squamous cell carcinoma of the head and neck. Survival rates are further decreased in patients with nodal metastases that have spread beyond the lymph node capsule, or extracapsular spread (ECS). To the authors' knowledge, this is the first report on the impact of ECS in a large series of patients treated for squamous cell carcinoma of the oral tongue (SCCOT) at a single institution using surgery as the primary treatment modality. METHODS. The authors retrospectively reviewed the medical records of all patients treated for SCCOT with resection of the primary and neck dissection at a single institution between 1980 and 1995. RESULTS. Two hundred sixty-six patients were included in the study. Of that number, 146 patients (55%) were pathologically node-negative (pN0), 75 patients (28%) were pathologically node-positive (pN+) without ECS (pN+/ECS-), and 45 patients (17%) were pN+ with ECS (pN+/ECS+). The 5-year disease-specific and overall survival rates for pN0 patients were 88% and 75%; for pN+/ECS- patients, 65% and 50%; and 48% and 30% for pN+/ECS+ patients. The patterns of failure for the pN0, pN+/ECS- and, pN+/ECS+ groups showed overall recurrence rates of 19.8%, 34.2%, and 51.1% with regional failure rates of 11.5%, 19.2%, and 28.9%, respectively, and distant metastases rates of 3.3%, 8.2%, and 24.4%. CONCLUSIONS. ECS is the most significant predictor of both regional recurrence and development of distant metastasis accounting for decreased survival of patients with SCCOT in the current study. Therefore, intensive regional and systemic adjuvant therapy may be indicated for patients with ECS. Future studies should focus on identifying molecular mediators involved in ECS to determine targets for adjuvant therapies in this subset of patients.

Alveolar soft part sarcoma

Abstract: Alveolar soft part sarcoma (ASPS) is a rare sarcoma that typically arises in the lower extremity in adolescents and young adults between 15 and 40 years of age. Distribution by age and site in adults is shown in Figs. 17.1 and 17.2 for all adult ASPS. In children, a number of cases arise from the tongue and orbit, where it can be confused to some degree with embryonal rhabdomyosarcoma. ASPS is extremely rare, even at referral centers, which have been hard pressed to identify more than one to two patients a year per center in published series [1–3]. It frequently presents with innumerable small, round metastatic lesions in the lungs and shows a very slow rate of progression, one reason for the late presentation of what is often a primary >10 cm in greatest dimension. Progression is typically slow, but ultimately taking the patient’s life after 10–15 years of metastatic disease. Brain metastases are a particular feature of ASPS, with an incidence at least thrice of that of other sarcomas in one series and documentation in other series [4–7].

Des-gamma-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients.

Abstract: BACKGROUND Portal venous invasion (PVI) in patients with hepatocellular carcinoma (HCC) is an important factor affecting prognosis. The objective of this study was to elucidate predisposing factors for the development of PVI. METHODS Two hundred twenty-seven patients with HCC who did not show PVI and who received percutaneous ethanol injection therapy and/or microwave coagulation therapy at the time of their first hospital admission were enrolled between 1994 and 1996. After their HCC was treated, the patients were followed for a mean of 19 months. For the detection of HCC recurrence and/or development of PVI, ultrasonography was performed every 3 months, a computed tomography (CT) scan was performed every 6 months, and the biochemical parameters of the patients were measured every month. PVI was defined as protrusion of the tumor into the first and/or second branch or into the main trunk of the portal vein. RESULTS Of the 227 patients, 24 (11%) later developed PVI. Tabular analysis was performed on these 24 patients and indicated that tumor size, albumin, total bilirubin, prothrombin time, α-fetoprotein (AFP) level, and des-γ-carboxy prothrombin (DCP) level differed significantly between the time of initial admission and the time of PVI development. A univariate analysis performed on the 227 patients indicated that an increase in the numbers of tumors, the histologic tumor grade (differentiation), the AFP level, and the DCP level at the time of initial diagnosis of HCC had a significant correlation with the later development of PVI; and a stepwise, multivariate Cox regression analysis revealed that the DCP level was the strongest predisposing factor (P < 0.0010; risk ratio = 5.65) followed by the histologic grade of tumor differentiation. CONCLUSIONS The results suggest that the serum DCP level is the most useful predisposing clinical parameter for the development of PVI. Cancer 2001;91:561–9. © 2001 American Cancer Society.