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PubMed2006

Intraarterial chemotherapy as an adjuvant treatment in locally advanced gastric cancer.

BACKGROUND AND AIMS: D2 gastrectomy has improved survival in gastric cancer. Adjuvant intravenous chemotherapy, radiotherapy, or multimodal therapy has failed to demonstrate improved survival. The results of intraarterial chemotherapy (IARC) as an adjuvant have been encouraging in a few studies. A prospective randomized trial was designed to evaluate the toxicity and survival in locally advanced gastric cancer using IARC as an adjuvant after potentially curative gastrectomy. PATIENTS AND METHODS: Forty patients with locally advanced gastric cancer were randomly selected to undergo either potentially curative gastrectomy and receive IARC (study group) or gastrectomy only (control group). Clinical and histopathologic data were analyzed and the toxicity related to IARC was recorded. RESULTS: The groups were comparable (p>0.05). Three patients in the study group had minor toxicity. Five-year survival rate for the study and the control group was 52 and 54%, respectively (p>0.05). Mean survival for the study and the control group was 50+/-8 and 62+/-10 months, respectively (p>0.05). The number of recurrences and the failure sites were comparable (p>0.05). CONCLUSION: Intraarterial chemotherapy can be safely applied to gastric cancer patients. As proposed by the protocol, the method cannot be recommended as an adjuvant treatment for locally advanced tumors because it appears that there is no survival benefit compared to potentially curative gastrectomy alone.

Aged↗

PubMed2006

Visualizing syntenic relationships among the hemiascomycetes with the Yeast Gene Order Browser.

The Yeast Gene Order Browser (YGOB) is an online tool designed to facilitate the comparative genomic visualization and appraisal of synteny within and between the genomes of seven hemiascomycete yeast species. Three of these genomes are polyploid, and hence contain intra-genomic syntenic regions, the correct assembly of which is a particular success of YGOB. Designed to accurately assemble, display and score gene order relationships, YGOB is both an interactive tool for browsing genomic data, and a software engine now being used for evolutionary analyses on a whole-genome scale. Underlying the online interface is the YGOB database, which consists of homology assignments across the species, extensively curated based on sequence similarity and novelly, an appraisal of genomic context (synteny) in multiple genomes. Currently the YGOB database incorporates genome data from Saccharomyces cerevisiae, Candida glabrata, Saccharomyces castellii, Ashbya gossypii, Kluyveromyces lactis, Kluyveromyces waltii and Saccharomyces kluyveri, but the system is scaleable to accommodate additional genomes. This paper discusses the usage and utility of version 1.0 of YGOB, which is publicly available at http://wolfe.gen.tcd.ie/ygob.

Chromosomes, Fungal↗

PubMed1982

Work satisfaction and physical health.

This analysis asks how satisfaction with one's main work role (whether that is a paid job or housework) is related to physical health. Data from a Detroit survey show that: (1) Dissatisfied people have poorer health status and take more curative health actions than do satisfied people. The dissatisfied people have higher health risks due to more smoking, drinking, and stress, and they also have health attitudes that encourage symptom perception. Poorer health explains why they take more curative actions; they actually have less faith in the value of medical care and restricted activity and less access to care than do satisfied people. (2) Work satisfaction is more important for nonemployed people than employed ones. Dissatisfied homemakers have especially numerous symptoms and high drug use. And dissatisfied, nonemployed men report a great deal of recent restricted activity and medical care. The data suggest that the homemakers focus on their day-to-day symptoms and try to relieve them by drugs; on the other hand, poor health has forced the men to quit work, and they are very unhappy about the situation. (3) Women (whether they are employed or homemakers) are more sensitive to work satisfaction than are employed men. Apparently employed men adjust better to job stresses and suffer few health consequences, whereas women cannot buffer their dissatisfactions as well. In summary, the Detroit data indicate that work satisfaction is related to good health for both sexes, and that being a dissatisfied homemaker poses especially high risks of poor health.

Adult↗

PubMed2006

Long-term follow-up after transoral laser microsurgery and adjuvant radiotherapy for advanced recurrent squamous cell carcinoma of the head and neck.

PURPOSE: The aim of this study was to evaluate the efficacy of adjuvant radiotherapy after transoral laser microsurgery for advanced recurrent head-and-neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Between 1988 and 2000, 37 patients with advanced local recurrences (23 local and 14 locoregional recurrences) of HNSCC without distant metastases were treated in curative intent with organ-preserving transoral laser microsurgery and adjuvant radiotherapy (before 1994 split-course radiotherapy with carboplatinum, after 1994 conventional radiotherapy). Initial therapy of the primary (8.1% oral cavity, 35.1% oropharynx, 13.5% hypopharynx, and 43.3% larynx) before relapse was organ-preserving transoral laser microsurgery without any adjuvant therapy. RESULTS: After a median follow-up of 124 months, the 5-year overall survival rate was 21.3%, the loco-regional control rate 48.3%, respectively. In multivariate analysis, stage of original primary tumor (Stage I/II vs. Stage III/IV), and patient age (<58 years vs. >or=58 years) showed statistically significant impact on prognosis. In laryngeal cancer, larynx preservation rate after treatment for recurrent tumor was 50% during follow-up. CONCLUSION: Our data show that organ-preserving transoral laser microsurgery followed by adjuvant radiotherapy is a curative option for patients who have advanced recurrence after transoral laser surgery and is an alternative to radical treatment.

Adult↗

PubMed2004

Decreased interleukin-1 receptor antagonist response following moderate exercise in patients with colorectal carcinoma after primary treatment.

Clinical and experimental studies have shown that a moderately increased physical activity level may have beneficial effects in terms of exercise conditioning, resistance to infection and decreased relative risk of cancer. Modulation of the innate and adaptive components of the immune system with a shift of cytokines and their antagonists to a more pro- and less anti-inflammatory response was found to be a prominent feature in non-tumor patients and healthy volunteers. As quantitative data concerning the cytokine/antagonist response following exercise are not available for tumor patients, we compared the effects of a post-operative rehabilitation program with moderate exercise (ME) intensity (0.55-0.65 x maximal aerobic power) with a program with low exercise (LE) intensity (0.30-0.40 x maximal aerobic power) in patients with curatively treated colorectal carcinoma (UICC II and III) measuring pro- (IL-1beta, IL-6, tumour necrosis factor (TNF)) and anti-inflammatory cytokines (IL-1 receptor antagonist, sTNF receptors I and II). Twenty-three patients participated in this prospective trial, N = 13 in the ME group, N = 10 in the LE group. Exercise was performed daily 30-40 min for 2 weeks. Basal (circulating) and LPS-stimulated (phasic) cytokine and antagonist response was determined before exercise and after 1 and 2 weeks using appropriate ELISA tests. The LPS-stimulated interleukin-1 receptor antagonist (IL-1ra) response in the ME group gradually decreased from 31,532.6 (160.0-70,028.0) to 18,033.0 pg/ml (5040.0-52,570.0) after one and to 22,892.0 pg/ml (6376.0-34,726.0) after 2 weeks (P < 0.05) with a concomitant decrease of the corresponding IL-1ra/IL-6 and IL-1ra/IL-1beta ratio: 2.51-1.41 and 4.1-3.1, respectively. In contrast, in the LE group LPS-stimulated cytokines and antagonists did not significantly change during exercise. Circulating cytokines and antagonists remained unchanged in both groups. In providing quantitative data in patients with curatively-treated colorectal cancer, we demonstrated that a short-term rehabilitation program with moderate exercise leads to a decreased LPS-induced antagonist response with a shift to a more pro-inflammatory state (decreased antagonist/cytokine ratio). Whether this change of the phasic immune response to moderate exercise may be clinically beneficial (decreased rates of infection, relapses and/or second tumours) is possible, but has to be investigated in long-term studies.

Adenocarcinoma↗

PubMed2004

Laparoscopy as a prognostic factor in curative resection for node positive colorectal cancer: results for a single-institution nonrandomized prospective trial.

BACKGROUND: Several studies reporting preliminary long-term survival data after laparoscopic resections for colonic adenocarcinoma did not show any detrimental effect in comparison with historic studies of laparotomies. A previous randomized study has reported an unforeseen better long-term survival for node-positive patients treated by laparoscopic colectomy. METHODS: A single-institution prospective nonrandomized trial compared short- and long-term results of laparoscopic and open curative resection for adenocarcinoma of the left colon or rectum in 255 consecutive patients from January 1996 to December 2000. RESULTS: In this study, 34 left hemicolectomy, 202 anterior resections, and 19 abdominoperineal resections were performed. A total of 74 patients underwent a laparoscopic resection (LR), and 181, an open resection (OR). The tumor site was the descending colon in 32 cases, the sigmoid colon in 98 cases, and the rectum in 125 cases, including 87 mid-low rectal cancers. Ten LR procedures (13.5%) were converted to open surgery. The hospital mortality was 0.08%, and in hospital morbidity was 16.2% for LR and 13.3% for OR (p = 0.56). The median postoperative stay was 1 day shorter for LR (9 days) than for OR (10 days) (p = 0.09). The mean number of lymph nodes retrieved were 13.8 +/- 5.7 for OR and 12.7 +/- 5; for LR (p = 0.23). Age exceeding 70 years, T stage, N stage, grading, mid-low rectal site, and laparoscopy were found by multivariate analysis to be significant prognostic factors for disease-free and cancer-related survival. When patients were stratified by stage, a trend toward a better disease-free and cancer-related survival was identified in stage III patients undergoing LR. CONCLUSIONS: Laparoscopic colonic resection is a safe procedure in terms of postoperative outcome and long-term survival. Multivariate analysis showed that laparoscopy is a positive prognostic factor for disease-free and cancer-related survival. The current data agrees with the data for the only randomized study reported so far. Both suggest a better outcome for node-positive patients treated by laparoscopy.

Adenocarcinoma↗

PubMed2003

[Limitations of laparoscopic visceral surgery in oncology].

Controversial discussion focuses on the application of laparoscopic curative resection for cancer due to oncologic radicality,tumor cell dissemination, and port site metastases. Considering the limitations of laparoscopic surgery, it is necessary to objectively evaluate whether laparoscopic surgery is associated with an improved quality of curative treatment. Therefore, controlled studies comparing the results of laparoscopic vs conventional cancer surgery are mandatory. To date, comparable findings on short-term outcome of laparoscopy with open resection can only be shown for colorectal cancer. However, long-term data including recurrence and survival are still missing as randomized studies (phase IIIb) are still to be completed. Consequently, laparoscopic curative resection should only be performed within controlled trials. In terms of the upper GI tract, minimally invasive surgery has proven to be technically feasible in expert centers including limited resections for early gastric cancer, left pancreatectomies, or hepatic resections for malignancy. Finally, laparoscopy has gained acceptance in the field of diagnosis (e.g., staging laparoscopy, laparoscopic ultrasound) and palliative treatment (e.g. gastroenterostomy, thermoablation) without the need for controlled studies.

Colorectal Neoplasms↗

PubMed2026

ToxiVerse: chemical bioprofiling, toxicity data sharing and customizable predictive modeling.

MOTIVATION: Chemical toxicity assessment is critical for drug development and environmental safety. Computational models have emerged as a promising alternative to animal testing and now play a significant role in efficiently evaluating new chemicals. To address the urgent need for user-friendly machine learning tools in computational toxicology, we developed ToxiVerse, a public web-based platform. RESULTS: ToxiVerse provides automatic chemical bioprofiling, curated toxicity datasets, and a predictive modeling interface designed for researchers who lack programming expertise. The platform comprises three integrated modules: (i) Bioprofiler, which provides chemical descriptors by combining chemical-bioactivity data from PubChem assays with a machine learning-based data gap-filling procedure; (ii) Database, which hosts ∼50 000 curated chemicals covering diverse toxicity endpoints; and (iii) Cheminformatics, which enables dataset upload, chemical curation, and automatic generation of quantitative structure-activity relationship models for toxicity prediction. AVAILABILITY: The tool is accessible at www.toxiverse.com, and source code is available at https://github.com/zhu-research-group/toxiverse.

Quantitative Structure-Activity Relationship↗

PubMed1985

Radiation treatment of carcinoma of the vulva, 1950-1980.

A retrospective study of all patients with carcinoma of the vulva treated by radiation therapy at the A. Maxwell Evans Clinic of the Cancer Control Agency of British Columbia, between 1950 and 1980, is reported. Sixty-eight patients, representing 30% of all referred patients with vulvar cancer, were analyzed for survival, recurrence patterns, complications, and clinical features. This group is companion to a series of patients treated with operation reported in 1979. The data confirm a major role for radiation therapy both in palliation and in combined radiotherapy-operation. For 13 cases, radiotherapy with curative intent was used in combination with operation resulting in a 5-year actuarial survival of 92%, with acceptable posttreatment morbidity. The advantages of preoperative radiotherapy, particularly for posterior vulvar lesions, are suggested by the data, and the need for a reappraisal of the role of radiotherapy in vulvar carcinoma is stressed.

Actuarial Analysis↗

PubMed1995

[Prognostic factors in curative resection of stomach carcinoma. A uni- and multivariate analysis].

The TNM system, including tumor infiltration (T category), lymph node infiltration (N category) and metastasis (M category), is a well-established system of prognostic factors. To evaluate the prognostic importance of patient characteristics and tumor parameters 5 clinical and 13 pathological factors were analyzed. Data on 200 consecutive patients with histologically verified stomach cancer were prospectively recorded using a standardized form. In the subgroup with curative resection (R0, n = 108) a uni- and multivariate analysis was performed with respect to 5-year survival. In the univariate analysis statistical significance was demonstrated for the following factors: tumor size, tumor localization, T category, N category, number of infiltrated lymph nodes infiltrated, lymph node compartments, tumor stage, lymph node ratio: infiltrated/inspected. Multivariate analysis, taking into consideration the interaction between prognostic factors, revealed only two factors as statistically significant: number of infiltrated lymph nodes and tumor size. Our results and those in the literature indicate that the infiltration of lymph nodes is the most relevant prognostic factor. In addition to the TNM system the number of infiltrated lymph nodes seems to be of prognostic importance.

Adult↗

PubMed2005

Gallbladder carcinoma with biliary invasion: clinical analysis of the differences from nonbiliary invasion.

Gallbladder carcinoma is the most common malignancy of the biliary tract. Because of a lack of specific presentations, this condition frequently is diagnosed only at an advanced stage. The clinical difference between gallbladder carcinoma with and without biliary involvement remains uncertain. This study recruited all patients with gallbladder carcinoma treated at Chang Gung Memorial Hospital (Taoyuan, Taiwan) from 1987 to 2002. The sample included 120 patients aged 28 to 91 years (mean 65.5 +/- 12.3 years) (39 men, 81 women), whose medical records were reviewed retrospectively. Based on the 2002 newly revised TNM classification, 25, 38, 28, and 29 patients had stage I, II, III, and IV disease, respectively. After we excluded patients with stage I, the other patients were classified into two groups as follows: group I, gallbladder carcinoma with biliary invasion (n = 41); group II, carcinoma without biliary involvement (n = 54). The clinical presentations, laboratory data, operative methods, and outcome of these two groups were compared. The two groups did not differ in terms of age, sex distribution, cholelithiasis, and most clinical presentations. Chemistry laboratory data also identified patients in group I with significantly elevated liver function tests. Group II had a borderline tendency toward better curative resectability than group I (p = 0.09). Survival was significantly better for group I patients who underwent curative resection (n = 5) via cholecystectomy, partial hepatectomy, and bile duct resection than for those with noncurative resection (p < 0.05). However, long-term survival demonstrated that gallbladder carcinoma had the same poor prognosis in the two groups. In conclusion, gallbladder carcinoma with biliary invasion has been found to a more overt clinical presentation and abnormal laboratory data, which might alert clinicians to consider gallbladder carcinoma at an advanced stage or biliary invasion and examine the underlying disease. Generally, the outcome of gallbladder carcinoma is dismal, and radical curative resection combined with cholecystectomy, partial hepatectomy, and bile duct resection perhaps may offer good benefits for advanced gallbladder carcinoma. Furthermore, surgical resection should be performed whenever possible in patients with gallbladder carcinoma to increase life expectancy.

Adult↗

PubMed1996

Gastric carcinoma: does lymph node dissection alter survival?

BACKGROUND: Extragastric lymphadenectomy (D2 node dissection) is strongly supported by Japanese data to have survival benefit. Randomized trial data are either inconclusive or nonsupportive of this view. We have reviewed a prospectively gathered database of 18,346 cases of gastric carcinoma from a gastric cancer patient care evaluation study conducted by the American College of Surgeons to assess whether the performance of extragastric node dissection was associated with improved survival in patients who had resection with curative intent (all margins microscopically clear). STUDY DESIGN: We reviewed a subgroup of patients with curatively resected gastric carcinoma and compared the outcome in patients having extragastric lymph node dissection with the outcome in patients who did not have dissection of N2 nodes. RESULTS: Among the 3,804 patients having curative resection in the long-term study with more than a five-year follow-up, 695 had dissection of the nodes along the celiac axis, hepatic artery, or splenic artery (N2 nodes); 1,529 patients had removal of the adjacent nodes (N1 nodes) along the gastric tube or the gastric or perigastric nodes (N1 nodes); and 903 patients who had no nodes identified in the resection specimen (essentially N0 nodes removed). For patients having a dissection of N2 nodes, the median survival time was 19.7 months with a five-year survival rate of 26.3 percent; for patients having a dissection of N1 nodes, the median survival time was 24.8 months with a five-year survival rate of 30 percent; among patients having no nodes removed, the median survival time was 29.5 months with a five-year survival rate of 35.6 percent. CONCLUSIONS: Lymph node dissection (D2) of N2 nodes did not augment survival compared with gastrectomy without node dissection or that included perigastric nodes in the resection. Subgroup analysis of patients with gastric carcinoma having a curative resection did not show benefit of the extragastric node dissection (D2). Continued study is warranted and the data from ongoing clinical trials may yield more conclusive information.

Aged↗

PubMed2006

Endoscopic resection of benign tumors of the papilla of vater.

Most benign papillary tumors are adenomas which can potentially undergo the adenoma-carcinoma-sequence making complete removal mandatory for curative therapy. Endoscopic resection (papillectomy) of these lesions is being increasingly performed as a less traumatic alternative to surgery. Available data shows endoscopic papillectomy to be effective and safe in experienced hands with usually little morbidity and virtually no mortality. Success rates are around 80 % for lesions without intraductal involvement. Selected cases of limited distal intraductal involvement accessible after sphincterotomy may also be managed curatively by endoscopic resection. Endoscopic snare resection of entire lesions should be primarily regarded as a diagnostic procedure. It allows for an accurate histological diagnosis based on examination of the entire specimen rather than forceps biopsies and thus a reliable assessment of the need for surgical therapy. Subsequent surgery in operable patients is not precluded by previous endoscopic resection. Surgery is indicated in case of incomplete removal and if malignancy is present. The curative role of endoscopic papillectomy for early invasive carcinoma needs to be established. Histological features and individual risk for surgery are factors to be considered. Inoperable patients may still benefit from palliative endoscopic stenting. After endoscopic papillectomy has been completed, regular follow-up examinations including biopsies are warranted because of the risk of local recurrence. For benign looking papillary tumors, endoscopic papillectomy serves as a diagnostic tool and should be considered as first line procedure regardless of age. The following article details the approach to patients with benign papillary tumor and the technique of endoscopic papillectomy.

Ampulla of Vater↗

PubMed2025

BAV-LLPS: a database of bacterial, archaea, and virus liquid-liquid phase separation proteins.

MOTIVATION: Liquid-liquid phase separation (LLPS) is a key process underlying the formation of biomolecular condensates, such as membrane-less organelles, that compartmentalize biochemical processes inside the cells. While LLPS has been extensively studied in eukaryotes, its role in bacteria, archaea, and viruses remains far less characterized. Recent studies in bacteria have revealed that LLPS-driven condensates play critical roles in RNA processing, stress response, and pathogenicity. Similarly, many viruses exploit LLPS to facilitate crucial steps in their infection cycles, including viral entry, genome replication, assembly, and host immune evasion. RESULTS: In this work, we introduce a hand-curated database of LLPS proteins from bacteria, archaea, and viruses (BAV-LLPS Database). This resource, extended through sequence similarity searches, comprises over 5000 proteins and integrates diverse data including biological annotations, sequence features, predicted disordered regions, LLPS per site probability, and AlphaFold2-based structural models. Additionally, our web server enables users to explore both the curated and homologous derived datasets, providing a platform to uncover evolutionary relationships and intrinsic and differential properties of LLPS proteins across various taxonomic groups. This work seeks to deepen our understanding of LLPS mechanisms beyond eukaryotic organisms, emphasizing their significance across diverse life forms. It also aims to foster the development of specialized predictive tools that will facilitate the exploration and characterization of LLPS processes in a wide array of living organisms, thereby contributing to advancements in both fundamental biological research and applied biomedical sciences. AVAILABILITY AND IMPLEMENTATION: BAV-LLPS DB is freely accessible at https://bav-llps-db.bioinformatica.org/. The data can be retrieved from the website. The source code of the database can be downloaded from https://bav-llps-db.bioinformatica.org/download.

Databases, Protein↗

PubMed1999

The Yeast Proteome Database (YPD): a model for the organization and presentation of genome-wide functional data.

The Yeast Proteome Database (YPD) is a model for the organization and presentation of comprehensive protein information. Based on the detailed curation of the scientific literature for the yeast Saccharomyces cerevisiae, YPD contains more than 50 000 annotations lines derived from the review of 8500 research publications. The information concerning each of the approximately 6100 yeast proteins is structured around a convenient one-page format, the Yeast Protein Report, with additional information provided as pop-up windows. Protein classification schema have been revised this year, defining each protein's cellular role, function and pathway, and adding a Functional to the Yeast Protein Report. These changes provide the user with a succinct summary of the protein's function and its place in the biology of the cell, and they enhance the power of YPD Search functions. Precalculated sequence alignments have been added, to provide a crossover point for comparative genomics. The first transcript profiling data has been integrated into the YPD Protein Reports, providing the framework for the presentation of genome-wide functional data. The Yeast Proteome Database can be accessed on the Web at http://www.proteome.com/YPDhome.html

Computational Biology↗

PubMed2005

Endoanal ultrasound-guided surgery for anal fistula.

BACKGROUND AND STUDY AIMS: Outcomes following surgical treatment of patients with anal fistula are related to eradication of tracts and the internal opening. In this study, the results of surgery based on endoanal ultrasound (EAUS) findings were evaluated. PATIENTS AND METHODS: A total of 102 patients with primary cryptogenetic anal fistula were prospectively examined with EAUS, using a 360-degree rotating 10-MHz probe, equipped with a three-dimensional (3-D) imaging system. Injection of hydrogen peroxide through the external opening was also used. Patients underwent operation on the basis of the EAUS findings. The agreement between findings from EAUS and from surgery was calculated. Clinical results were reported as treatment success, fistula recurrence, and fecal incontinence. RESULTS: Amongst 102 patients, the overall concordance between EAUS and surgical findings was 94.1 % for primary tracts, 91.2 % for internal openings, 96.1 % for secondary tracts, 100 % for abscesses, and 96.1 % for horseshoe tracts. Diagnostic accuracy was improved when hydrogen peroxide injection or 3-D imaging were used. Fistulotomy was performed in 46 patients (45.1 %), fistulectomy in 17 (16.7 %), fistulotomy plus seton placement in 19 (18.6 %), fistulectomy plus seton in 18 (17.6 %), and mucosal flap advancement in 2 (2.0 %). The operation was curative in 100 patients (98.0 %), and unsuccessful in 2 (2.0 %) due to recurrence of the fistula. Fecal continence was preserved in all patients. CONCLUSIONS: These data highlight the diagnostic accuracy of EAUS, particularly when hydrogen peroxide injection or 3-D imaging are used. Basing our surgical decision making on EAUS findings allowed us to carry out curative operations in a significantly large number of patients; the recurrence rate was very low. The accurate EAUS assessment of the relationship between fistulas and sphincters has been the main factor in choosing a sphincter-saving surgical procedure, avoiding fecal incontinence.

Adolescent↗

PubMed1994

Control of established experimental allergic encephalomyelitis by inhibition of tumor necrosis factor (TNF) activity within the central nervous system using monoclonal antibodies and TNF receptor-immunoglobulin fusion proteins.

Tumor necrosis factor (TNF) activity was inhibited during the development of actively-induced, chronic relapsing experimental allergic encephalomyelitis (CREAE) in Biozzi AB/H mice, using a mouse TNF-specific (TN3.19.12) antibody and bivalent human p55 and p75 TNF receptor-immunoglobulin (TNFR-Ig) fusion proteins. The development of disease could be inhibited when repeated doses of antibody were administered prior to the anticipated onset. It has now also been shown that a therapeutic effect is evident even when antibody is administered after the onset of clinical signs, further indicating an important role for TNF in pathogenic effector mechanisms in CREAE. Although biologically-active TNF was not detected in the circulation, TNF-alpha was detected in lesions within the central nervous system (CNS). This suggested that the CNS may be the main site for TNF-specific immunomodulation and was supported by the observation that intracranial injection was significantly more potent than that administered systemically, for both antibody and TNFR-Ig fusion proteins. The fusion proteins were as effective as antibody at doses 10-100-fold lower than that used for antibody, reflecting their higher neutralizing capacity in vitro. Although treatment was not curative and relapse inevitably occurred in this model if treatment was not sustained, the data indicate that anti-TNF immunotherapy, especially within the CNS, can inhibit CREAE and may, therefore, be useful in the control of human neuroimmunological diseases.

Animals↗

PubMed1998

Radiochemotherapy as an adjuvant treatment for rectal cancer.

Adjuvant treatment with radiotherapy has been proposed in rectal cancer surgery, due to the high local recurrence rate. However, the rate varies substantially in the literature, an this may be one reason that adjuvant treatment is not obvious to all surgeons. The difference may be due to selection bias, different criteria for curative surgery, different follow-up routines, and/or the skill of the surgeon. The data are unequivocal from all randomized trials comparing surgery alone with surgery plus radiotherapy, given either pre- or postoperatively: the average local recurrence rate is about 29% in the surgery-alone arm. With pre- or postoperative radiotherapy the local recurrence rate is more or less halved. Moreover, preoperative irradiation is more dose efficient than postoperative irradiation, indicating that a higher dose must be used when postoperative radiotherapy is delivered, with an increased risk of damaging the normal surrounding tissues in the pelvis. This damage of normal tissue also has an impact on sphincter function and on postoperative small bowel obstruction. Since preoperative radiotherapy is more effective in killing tumor cells at a lower dose than postoperative treatment with or without chemotherapy, and since preoperative treatment is less toxic to normal tissues, preoperative radiotherapy should be used whenever radiotherapy for rectal cancer is considered.

Chemotherapy, Adjuvant↗