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Definitive therapy for prostate carcinoma: Mayo Clinic results at 15 years after treatment.

Data on long-term follow-up for definitive therapy of prostate cancer are limited, especially for radiation therapy. Either surgery or radiation was used in 322 patients for treatment with curative intent, and follow-up was for a minimum of 15 years. Overall survival was nearly identical to that in age-matched cohort. 5-, 10-, and 15-year recurrence-free survival rates were 77%, 63% and 53%, respectively. Grade and stage were significant prognostic factors for both recurrence and survival. More than 60% of the initial failures were local, and more than 25% of the failures occurred after 10 years. Radiation therapy was used in 137 patients with clinically staged disease. Radical retropubic prostatectomy and perineal prostatectomy were performed in 133 and 44 patients, respectively. In this group, pathological staging was used. Survival rates for surgically treated patients were better than those in the cohort population. In conclusion, overall long-term follow-up demonstrates that definitive treatment does not have an adverse effect on survival from prostate cancer. Local recurrence is a frequent cause of failure. Caution must be used in interpreting any prostate study with less than 10 years of follow-up, because 25% to 50% of the failures occur after that time.

Aged↗

Textpresso: an ontology-based information retrieval and extraction system for biological literature.

We have developed Textpresso, a new text-mining system for scientific literature whose capabilities go far beyond those of a simple keyword search engine. Textpresso's two major elements are a collection of the full text of scientific articles split into individual sentences, and the implementation of categories of terms for which a database of articles and individual sentences can be searched. The categories are classes of biological concepts (e.g., gene, allele, cell or cell group, phenotype, etc.) and classes that relate two objects (e.g., association, regulation, etc.) or describe one (e.g., biological process, etc.). Together they form a catalog of types of objects and concepts called an ontology. After this ontology is populated with terms, the whole corpus of articles and abstracts is marked up to identify terms of these categories. The current ontology comprises 33 categories of terms. A search engine enables the user to search for one or a combination of these tags and/or keywords within a sentence or document, and as the ontology allows word meaning to be queried, it is possible to formulate semantic queries. Full text access increases recall of biological data types from 45% to 95%. Extraction of particular biological facts, such as gene-gene interactions, can be accelerated significantly by ontologies, with Textpresso automatically performing nearly as well as expert curators to identify sentences; in searches for two uniquely named genes and an interaction term, the ontology confers a 3-fold increase of search efficiency. Textpresso currently focuses on Caenorhabditis elegans literature, with 3,800 full text articles and 16,000 abstracts. The lexicon of the ontology contains 14,500 entries, each of which includes all versions of a specific word or phrase, and it includes all categories of the Gene Ontology database. Textpresso is a useful curation tool, as well as search engine for researchers, and can readily be extended to other organism-specific corpora of text. Textpresso can be accessed at http://www.textpresso.org or via WormBase at http://www.wormbase.org.

Abstracting and Indexing↗

Clinical practice guidelines: renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is the most common renal malignancy and is increasing at an annual rate of approximately 2% worldwide. Metastatic RCC is among the more chemotherapy-refractory malignancies, with a 5-year survival rate less than 2%. A variety of therapies are currently under investigation for the treatment of metastatic RCC, particularly involving immunotherapeutic agents such as interferon alfa. OBJECTIVES: To review and compare historical and current data that define practice guidelines in the treatment of RCC. DISCUSSION: Of the various treatment modalities available for RCC, only surgery with complete removal of tumor burden can be considered as potentially curative, since the tumor is resistant to chemotherapy, hormonal therapy, and radiation therapy. However, biologic response modifiers (BRMs)-particularly immunotherapeutic agents such as interferon alfa-have been extensively studied and appear to produce objective tumor regression in selected patients with advanced disease. CONCLUSIONS: In patients with metastatic RCC, performance status is the most important predictor of outcome, and should therefore be utilized for therapeutic decision making. Immunotherapy with BRMs such as recombinant interferon alfa and recombinant interleukin-2 has been associated with meaningful antitumor responses in selected patients. Combination therapy with recombinant interferon alfa, recombinant interleukin-2, and 5-fluorouracil may offer considerable promise, and the subcutaneous administration of recombinant interferon alfa and recombinant interleukin-2 may improve the tolerability and convenience of these cancer treatments by reducing side effects and permitting outpatient administration. As treatment expectations for metastatic RCC are limited, experimental approaches are warranted.

Carcinoma, Renal Cell↗

[Descriptive and analytical epidemiology of second primaries in Osaka, Japan].

With the improvement in survival of cancer patients, the incidence of second primaries has been increasing. Data from the Osaka Cancer Registry showed that the incidence of metachronous second primaries was associated with gender (male), age and calendar year at diagnosis of the first cancer. The 10-year cumulative risk was estimated at around 10% for those who developed their first cancer in their sixties in 1978-83. The observed number (O) of second primaries (including synchronous) was compared with the expected number (E). The O/E ratios among those who developed their first cancer at ages 0-14 and 15-29 years old were much higher than the ratios among all age groups. Patients who had developed cancer of the colon, larynx, lung, bladder, or breast (1978-86) showed a significantly higher than expected risk of developing second primaries during the 1-4 years after diagnosis of the first cancer. Based on the hospital cancer registry data from Osaka Medical Center for Cancer and Cardiovascular Diseases, associations between adjuvant chemo-immunotherapy and the risk of second primaries were examined among 1,925 gastric cancer patients who underwent curative gastrectomy. The sex-, age-, and stage-adjusted hazard rate ratio of second primaries was 1.04 for patients who underwent chemotherapy and 0.70 for patients who underwent chemo-immunotherapy, when compared with the risk for patients who did not receive adjuvant chemo-immunotherapy. Some chemotherapeutic agents appeared to increase the risk of second primaries. Second primaries among 2,824 breast cancer patients were examined and their associations with adjuvant chemo-immuno-radiotherapy were analyzed. The O/E ratio for cancers of all sites was 1.28, significantly higher than 1.0. Cancer of the stomach, colon, lung and ovary were frequently observed as a second primary among them. Among 117 patients who developed second primaries, 4 developed cancer of the corpus uteri. This corresponded to 1.89 times the expected, however, only one of the 4 patients underwent tamoxifen treatment. The O/E ratio for non-Hodgkin's lymphoma was 3.40, significantly higher than 1.0. These results suggest associations between the risk for non-Hodgkin's lymphoma and chemotherapy.

Adult↗

Esophageal squamous cell carcinoma: the specific limited place of surgery defined by a prospective multivariate study of prognostic factors after surgical approach.

From 1982 to 1990, 181 patients underwent surgery for esophageal squamous cell carcinoma, for which 14 prognostic parameters were prospectively recorded in order to perform a multivariate study. A squamous cell head and neck cancer was associated with the esophageal tumor in 40% of the cases (synchronous 18% and metachronous 22%). Resection was curative (i.e. macroscopically complete) in 128 cases, palliative (i.e. with residual tumor) in 24 cases and not possible in 29 cases. There were 21 deaths in hospital (hospital mortality was 11.7%). One hundred and twenty-two patients received preoperative chemotherapy and 77 received postoperative radiotherapy according to different phase II prospective studies. The 5-year survival rate according to the Kaplan-Meier method was 15.8% (+/- 3.4) for all patients and 23.5% (+/- 4.8) for the patients who had a curative resection. A palliative resection or the invasion of a neighbouring organ was synonymous with incurability, but positive lymph nodes were not considered proof of incurability. The multifactorial study concerning all the patients highlighted two main prognostic parameters: the histological staging according to the Japanese classification (P = 0.0006) and the type of resection (curative or not) (P = 0.006). An objective response to preoperative chemotherapy was the third and last parameter revealed by Cox's model. The multivariate study, which was limited to the 112 patients who were alive after a curative resection, showed that only the stage was an important prognostic factor (P = 0.003), with stages 2 and 3 carrying a worse prognosis. We propose a therapeutic scheme, based on these prognostic data and on the usual pre-therapeutic workup with three additional exams: CT scan measurement of tumor diameter, ultrasound examination +/- fine needle aspiration cytology of supra-clavicular lymph nodes and echo-endoscopy. The aim of this scheme is to limit surgery to the subgroup of patients for whom this modality is really beneficial.

Adult↗

[Chemotherapy for patients with advanced/recurrent gastric cancer and the practice at our institute].

Chemotherapy results for all 157 patients with advanced/recurrent gastric cancer at our institute were analyzed based on survival duration. The median survival time (MST) of all 157 patients was 426 days. The break down of the 157 patients are as follows: 59 patients with recurrence after curative operation, 47 patients with a radical grade C after non-curative operation and 51 patients with unresectable gastric cancer, and whose MST's were 590, 610 and 215 days, respectively. The standard chemotherapy for advanced/recurrent gastric cancer has not been established. Our data showed that chemotherapy for gastric cancer should be performed as a means of clinical study. If the patients had any exclusion criteria of clinical study or a proper clinical study did not exist, we would have recommended the TS-1 based regimen as the first-line chemotherapy, and the taxane based regimen as the second-line chemotherapy.

Adult↗

Clinical impact of fluorine-18 fluorodeoxyglucose positron emission tomography in cancer patients. A comparative study between dedicated camera and dual-head coincidence gamma camera.

AIM: Positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) can be performed using a dedicated PET scanner (PET-I) or a dual-head coincidence gamma camera (CGC-I). The aim of this study was to comparatively assess the impact of PET-I and CGC-I on clinical management in cancer patients. METHODS: From November 2000 to November 2002, PET-I and CGC-I were performed at an interval of 2 days in 151 patients with colorectal cancer (n=40), breast cancer (n=28), thyroid cancer (n=23), lung tumors (n=22), germ cell tumors (n=14), unknown primary cancer (n=7) and other cancers (n=17). PET-I and CGC-I were interpreted independently with knowledge of conventional imaging (CI). In June 2003, theoretical management, e.g. treatment modality/ies and treatment intent (curative or palliative), after CI, PET-I and CGC-I were stated during multidisciplinary sessions and were a posteriori considered as appropriate or inappropriate using pathological and follow-up data. RESULTS: The theoretical management proposed after PET-I and after CGC-I was similar in 112/151 (74%; 95% CI: 66-81%) patients. In 125 assessable patients, theoretical management after PET-I was appropriate in 86% (95% CI: 79-92%), significantly higher (P=0.0033) than after CGC-I (70%; 95% CI: 62-78%). Both proportions were also higher than after CI (46%; 95% CI: 37-56%), (P<0.0001). A similar trend for higher proportions of appropriate management after PET-I than after CGC-I was observed for each tumor localization. CONCLUSIONS: The clinical impact of PET-I is superior to that of CGC-I in a large series of cancer patients. Although CGC-I could be considered as an acceptable alternative, PET-I remains the standard and should preferably equip nuclear medicine departments.

Adolescent↗

Discovering biomedical relations utilizing the World-wide Web.

To crate a Semantic Web for Life Sciences discovering relations between biomedical entities is essential. Journals and conference proceedings represent the dominant mechanisms of reporting newly discovered biomedical interactions. The unstructured nature of such publications makes it difficult to utilize data mining or knowledge discovery techniques to automatically incorporate knowledge from these publications into the ontologies. On the other hand, since biomedical information is growing explosively, it is difficult to have human curators manually extract all the information from literature. In this paper we present techniques to automatically discover biomedical relations from the World-wide Web. For this purpose we retrieve relevant information from Web Search engines using various lexico-syntactic patterns as queries. Experiments are presented to show the usefulness of our techniques.

Classification↗

[Indications for endoscopic treatment of early gastric cancer in the aged].

There are few data on the quality of life of patients with early gastric cancer before and after surgery or endoscopic treatment. We reported the long term effect of endoscopic laser therapy as a local curative procedure and discussed appropriate treatment of choice for early gastric cancer in the aged more than 70 years old based on the results of a comparative study of a group of 56 endoscopically treated group of patients and a group of 57 surgically treated patients. Fifty-six patients with endoscopically diagnosed early gastric cancer whose surgical risk was critical or who refused surgery were treated by either photocoagulative effect of Nd:YAG laser or photodynamic therapy with hematoporphyrin derivative and argon dye laser (PDT) or both. The efficacy (negative biopsy for cancer) of laser therapy is 73% at present. All the lesions of superficially elevated mucosal cancer less than 20mm and well demarcated flat or superficially depressed mucosal cancer less than 10 mm (10 elevated lesions, 8 flat or depressed lesions) were completely eradicated and negative for cancer on follow-up biopsy for more than 12 months. Risks of lymph-node metastasis in these lesions are reportedly negligible. Fourteen of the 56 patients (25%) treated by lasers died within 5 years after the initial therapy. Two of them died of gastric cancers too large to eradicate and were presumed to have submucosal invasion. On the other hand, 11 of 57 (19%) treated by surgery died within 5 years following surgery. One patient died from surgery and another of gastric cancer. Quality of life score did not decrease when the patients were treated by lasers but did so statistically significantly in the surgically treated group of patients. Although surgical death in the aged has decreased, death associated with surgical complications is significantly higher than with patients younger than 69 years old. Therefore, we conclude that endoscopic therapy is the treatment of choice for early gastric cancer as a local curative procedure in the aged, if they have a curable lesion as mentioned above.

Aged↗

Update in cancer chemotherapy: gastrointestinal cancer, cancer of the small intestines, gallbladder, liver, and esophagus.

This article updating cancer chemotherapy of gastrointestinal cancer completes the fivepart series begun in the April issue of the Journal. Treatment of cancer of the small intestine, the gallbladder and bile duct, primary cancer of the liver, and the esophagus are reviewed in this concluding article.Treatment of choice of cancer of the small intestine is surgical resection. Small bowel cancer is less responsive than gastric cancer to chemotherapy. While chemotherapy may produce temporary partial remissions in patients with gallbladder and bile duct cancer, there is no evidence that it produces longterm survival time. In primary liver cancer, surgery is the only curative treatment, but only 30 percent of patients are diagnosed with resectable lesions, and the surgical mortality rate is high. The most active single agents appear to be doxorubicin, fluorouracil, and neocarcinostatin. Data on combination chemotherapy are limited.With carcinoma of the esophagus, 95 percent of patients die of the condition. The standard treatment for locoregional disease is surgical resection and/or radiation therapy. Chemotherapy has been slow to develop; single-agent chemotherapy has been reported to be active in 15 percent of cases with durations of 2 to 5 months. Combination chemotherapy is so recent that data are incomplete as to long-term results of disease-free and total survival times, but polychemotherapy appears to be more effective than single agents.With earlier detection, prompt surgery, earlier chemotherapy, improved dose scheduling, and further exploration of combination therapy, better overall results with a major impact years later may be expected. Because of the lack of data, there remains uncertainty as to the place of chemotherapy in the treatment of gastrointestinal cancer.

Antineoplastic Agents↗

Advances in diagnosis and treatment of pancreatic cancer.

This review focuses on key advances in diagnosis and treatment of pancreatic cancer, with a particular emphasis on the expanding potential application of molecular techniques and the great strides made in evolving safe pancreatic resection. The epidemiology of pancreatic cancer is reviewed, and recent advances for potential screening are reported. Improvements in operative morbidity and mortality following pancreatic resection have led to calls for more radical surgery, and the results of conventional and extended radical surgery are compared. Recently combined multimodality adjuvant therapy has been used following "curative resection" for pancreatic cancer, and the current status concerning use of this treatment is addressed. Although there is insufficient evidence to recommend routine use of adjuvant therapy, there are sufficient encouraging data to advocate entering patients in large, adjuvant therapy trials. In addition to safe resectional surgery, advances in novel molecular therapy mean that the outlook for patients with pancreatic cancer should no longer be considered hopeless.

Chemotherapy, Adjuvant↗

The role of brachytherapy in the treatment and control of central bronchial carcinoma.

Endobronchial brachytherapy is by far the oldest interventional bronchiological treatment procedure. In the decades following its inception in 1922, it has undergone progressive modification by innovations in radiation physics and techniques, and has enjoyed a renaissance with the introduction of fibreoptic bronchoscopy, local anaesthesia, modern afterloading devices, and high dose rate (HDR) treatment with iridium-192, an isotope with very high activity. However, there is little standardization of dose-specification, fractionation and optimal dosage using this isotope, and homogeneous, objective analyses of the clinical results of treatment using iridium-192 is lacking. Very often, the exact staging of patients is lacking. For such reasons, any evaluation of the efficacy of endobronchial brachytherapy is significantly impeded. However, reliable data are available on the palliative effect of HDR-brachytherapy, which is safe, fast in onset and apparently superior to external beam radiotherapy (EBRT) alone. In addition, some studies document the curative effects, or complications, offers not only an insight into the working principles of radiation treatment but also into the biological behaviour of bronchial tumours. Endobronchial HDR-brachytherapy should be compared to the other interventional procedures focusing on the same aim, namely that of restoring patency of a previously occluded bronchus. This is the overall challenge to pneumologists working in this field.

Brachytherapy↗

[Physiotherapy methods in the rehabilitation of patients with cerebral vascular diseases].

The author has examined 650 patients aged 30-65 years with prestroke forms of cerebrovascular diseases. Basing on clinico-neurological, electrophysiological and biochemical data, five new variants of physiotherapy are proposed: transcerebral and segmental dalargin electrophoresis combined with magnetotherapy and manual therapy. Relevant practical recommendations are provided. The author's findings extend the knowledge of curative potential of physical methods and on their mechanism of action in cerebrovascular insufficiency.

Adult↗

[CO2 laser in pediatric laryngology].

Carbon dioxide Laser is a recently developed instrument which has became essential in laryngology, especially in its pediatric applications. Authors report 86 cases of children with a laryngeal pathology treated by CO2 Laser at the Childrens Hospital of La Timone in Marseille. Four groups emerge from this study. They are composed of laryngomalacia (n = 34), subglottic angiomas (n = 12), laryngeal papillomatosis (n = 12) and laryngeal stenosis (n = 14). Other patients (n = 14) made up a miscellaneous population (granulomas, laryngeal paralysis, benign tumors). Post-operative data are analyzed and compared with those of literature. The result is that this therapeutic method, used within the limits of precise indications and, if necessary, with divided sequences, can offer rapid curative care with few complications.

Adolescent↗

Mechanisms of transfusion-associated immunosuppression.

Many studies have reported allogeneic blood transfusions to be associated with adverse effects in recipients. These include a variety of transfusion reactions, graft-versus-host disease, alloimmunization, the transmission of infectious agents, and immunomodulation. In some instances the immunomodulatory effect has been reported to be beneficial to the recipient, i.e., recipients of renal allografts, individuals with Crohn's disease, and women with recurrent spontaneous abortions. Recent evidence indicates, however, that this autologous blood transfusion-associated immunomodulation might adversely affect the prognosis in patients with a malignancy as well as increase their risk for postoperative bacterial infection. The mechanisms of the autologous blood transfusion-associated immunosuppressive effect remain ill defined, although recent evidence indicates that such effects are probably due to the infusion of allogeneic donor leukocytes, or their products, present in the cellular blood products used for the transfusion. Recent experimental animal data indicate that this autologous blood transfusion-associated immunomodulatory effect can be ameliorated by the prestorage leukodepletion of allogeneic blood. Although data from animal experiments are useful in defining various in vivo biologic activities, properly designed prospective clinical trials are required to provide definitive indications as to whether patients with a malignancy undergoing curative surgery should receive leukodepleted allogeneic cellular blood products and the appropriate timing for such leuko-depletion.

Graft Rejection↗

PANTHER version 6: protein sequence and function evolution data with expanded representation of biological pathways.

PANTHER is a freely available, comprehensive software system for relating protein sequence evolution to the evolution of specific protein functions and biological roles. Since 2005, there have been three main improvements to PANTHER. First, the sequences used to create evolutionary trees are carefully selected to provide coverage of phylogenetic as well as functional information. Second, PANTHER is now a member of the InterPro Consortium, and the PANTHER hidden markov Models (HMMs) are distributed as part of InterProScan. Third, we have dramatically expanded the number of pathways associated with subfamilies in PANTHER. Pathways provide a detailed, structured representation of protein function in the context of biological reaction networks. PANTHER pathways were generated using the emerging Systems Biology Markup Language (SBML) standard using pathway network editing software called CellDesigner. The pathway collection currently contains approximately 1500 reactions in 130 pathways, curated by expert biologists with authorship attribution. The curation environment is designed to be easy to use, and the number of pathways is growing steadily. Because the reaction participants are linked to subfamilies and corresponding HMMs, reactions can be inferred across numerous different organisms. The HMMs can be downloaded by FTP, and tools for analyzing data in the context of pathways and function ontologies are available at http://www.pantherdb.org.

Animals↗

Dose-dependent metabolic response of mammary carcinoma to photodynamic therapy.

The metabolic response of mammary carcinoma in the C3H mouse to photodynamic therapy (PDT) was measured using in vivo 31P nuclear magnetic resonance (31P-NMR) spectroscopy and pH microelectrodes. Twenty-four hours after administration of Photofrin II (12.5 mg/kg), the tumor was subjected to photoactivation using an argon dye laser. Optical treatment doses were 200, 400, and 600 J/cm2 and corresponded to the following tumor control doses: TCD10/30, TCD50/30, and TCD90/30, respectively. In vivo 31P-NMR spectra and pH micro-electrode measurements were obtained prior to treatment and at 4, 24, 48, and 72 h and 1 week post-treatment. The data revealed a significant (P less than 0.0002) alkalosis as indicated by the pH measured by NMR compared to pH measured by microelectrodes at all treatment levels and time points. Spectral differences between treatment groups were apparent as early as 4 h after treatment. The ratio of beta-nucleoside triphosphate to inorganic phosphate at 4 h after treatment was significantly (P less than 0.01) smaller for 600 J/cm2 treatment than for 200 J/cm2 treatment. At curative (600 J/cm2) levels, from 48 h on, no phosphate resonances were detected in the spectra. The pH measured by NMR transiently decreased from pretreatment levels after 200 and 400 J/cm2 treatment (P less than 0.002, P less than 0.009, respectively), while no change in pH from pretreatment values was found after 600 J/cm2 treatment. The data suggest that the early metabolic response of mammary carcinoma to PDT, as indicated by 31P-NMR spectroscopy, is dose dependent, and may be a sensitive indicator of biological outcome to treatment.

Animals↗

Oncological outcome of ultra-low anterior resection with total mesorectal excision for carcinoma of the lower third of the rectum: Comparison of intrapelvic double-stapled anastomosis and transanal coloanal anastomosis.

BACKGROUND/AIMS: The purpose of this study was to determine whether the type of ultra-low anterior resection (intrapelvic double-stapled anastomosis or transanal hand-sewn coloanal anastomosis) with total mesorectal excision for primary adenocarcinoma of the lower third of the rectum affects survival and recurrence after curative surgery. METHODOLOGY: This retrospective study included 112 patients who underwent curative surgery achieved by ultra-low anterior resection in combination with either intrapelvic anastomosis using a double-stapling technique (DST group; n=82) or transanal hand-sewn coloanal anastomosis (CAA group; n=30). Univariate and corrected (multivariate regression) analyses were used to evaluate data. Median follow-up was 51.2 months for patients alive at the conclusion of this study. RESULTS: Disease-free and disease-specific survivals, and the frequency and location of recurrence after surgery did not differ between the two types of operations. Multivariate analyses showed that the type of operation was not a significant independent variable in predicting disease-free survival or in the development of both local and distant recurrences after surgery. Tumor-related factors (stage or histologic grade) were significant predictors of oncological outcome. CONCLUSIONS: The type of ultra-low anterior resection (DST or CAA) did not affect survival and recurrence after curative resection for carcinoma of the lower third of the rectum.

Adenocarcinoma↗