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[External radiotherapy with curative intent for adenocarcinoma clinically localized to the prostate (T1 to T3N0M0): intermediate results with a minimum follow-up of 4 years].

External beam radiation therapy is a well-established alternative to radical surgery for the treatment of clinically localized prostate cancer. However, many recent studies suggest that this treatment fails to eradicate prostatic tumors. Outcomes in 100 patients treated in a single institution are reported herein. Follow-up was at least four years in every case. Although survival rates were comparable to or greater than those reported in earlier studies, rates of local and distant recurrences were high, indicating poor treatment efficacy. These data suggest that radiation therapy is not an acceptable alternative to radical surgery for the curative treatment of localized prostatic carcinoma.

Actuarial Analysis↗

Is detection of asymptomatic recurrence after curative resection associated with improved survival in patients with gastric cancer?

BACKGROUND: It is not clear if more intense surveillance is associated with improved survival after curative resection for cancer. In the context of a followup program after curative gastrectomy, recurrence and survival were investigated for patients presenting with either symptomatic or asymptomatic recurrence. STUDY DESIGN: A prospectively maintained gastric cancer database was used to identify all patients who underwent a curative (R0) gastrectomy from July 1985 to June 2000. Survival curves were generated for patients with either symptomatic or asymptomatic recurrence, and the prognostic variables associated with outcomes were identified. RESULTS: Of 1,172 patients who underwent a curative (R0) gastrectomy, 561 patients (48%) had documented recurrence and 382 patients had complete data about symptoms. Median time to recurrence was 10.8months for asymptomatic patients and 12.4months for symptomatic patients (p = NS). Median postrecurrence survival was 13.5months for asymptomatic patients and 4.8months for symptomatic patients (p < 0.01). Median disease-specific survival was 29.4months for asymptomatic patients and 21.6months for symptomatic patients (p < 0.05). Variables predictive of poor postrecurrence survival included symptomatic recurrence, advanced stage (III/IV), poor differentiation, short disease-free interval (<12months), and multiple sites of recurrence. CONCLUSIONS: Followup did not identify asymptomatic recurrence earlier than symptomatic recurrence. Patients with symptomatic recurrence have more aggressive disease with a shorter postrecurrence survival. The impact of detecting asymptomatic recurrence in the course of followup after curative gastrectomy could not be distinguished from the effects of four powerful biologic variables that also interact to govern outcomes.

Adult↗

Reconciling gene expression data with known genome-scale regulatory network structures.

The availability of genome-scale gene expression data sets has initiated the development of methods that use this data to infer transcriptional regulatory networks. Alternatively, such regulatory network structures can be reconstructed based on annotated genome information, well-curated databases, and primary research literature. As a first step toward reconciling the two approaches, we examine the consistency between known genome-wide regulatory network structures and extensive gene expression data collections in Escherichia coli and Saccharomyces cerevisiae. By decomposing the regulatory network into a set of basic network elements, we can compute the local consistency of each instance of a particular type of network element. We find that the consistency of network elements is influenced by both structural features of the network such as the number of regulators acting on a target gene and by the functional classes of the genes involved in a particular element. Taken together, the approach presented allows us to define regulatory network subcomponents with a high degree of consistency between the network structure and gene expression data. The results suggest that targeted gene expression profiling data can be used to refine and expand particular subcomponents of known regulatory networks that are sufficiently decoupled from the rest of the network.

Computational Biology↗

[Construction of a recombinant baculovirus transfer vector with two promoters expressing the anti-human CD28 chimeric antibody by using TP-PCR method].

CD28, a cell surface glycoprotein, predominantly expressed on T cells, belongs to the Ig superfamily and provides critical co-stimulatory signals. The data which have published indicate that the monoclonal antibody against CD28 can decrease curative effects when it was applied in vivo for a long time. In order to avoid the human-anti-mouse action, anti-CD28 mAb must be humanized before it can be used in clinical study. Chimeric antibody, consisting of variable regions of mouse antibody and the constant regions of human IgG1, is often chosen by designers in generating humanized antibody. In this study, to prepare the anti-human CD28 chimeric antibody, the genes coding variable regions of anti-CD28 mAb and the constant regions of human IgG1 were cloned by PCR method. Then, the target genes were assembled by TP-PCR, a novel method developed for fusing genes without designing endonuclease sites at the both end of the target genes, and inserted into the baculovirus transfer vector pAcUW3 respectively. Thus, the recombinant baculovirus transfer vector with two strong promoters, ph and p10 was successfully constructed, which can express two different foreign genes at the same time. The recombinant vector was identified by the methods of restriction digesting, electrophoresis, PCR amplification and further verified by DNA sequence analysis. This work will contribute to expressing the chimeric CD28 antibody in insect cells.

Amino Acid Sequence↗

[Cystic pancreatic tumors--differential diagnosis, surgical therapy. Prognosis of cystic pancreatic tumors].

From 1986-2001 we treated 31 patients with cystic neoplasms of the pancreas. 13 patients showed a cystadenocarcinoma including one rare case of a serous cystadenocarcinoma. A curative resection (R0) was possible in 10 patients (resection rate: 76.9%). After median 61 months (range 29-144 months) 8 patients are alive without evidence of tumour. 2 patients died 2 months (pneumonia) and 36 months (local recurrence) respectively after operation. The latter case of tumour recurrence showed nodal involvement (pN1) in the Whipple specimen. One patient died 44 months after Whipple procedure with tumour-positive resection margin (R1 Situation) from local recurrence and hepatic spread. Our data reflect the good prognosis of cystic neoplasms of the pancreas reported in literature after curative resection--a result of the different biological behaviour compared with ductal adenocarcinome.

Adenocarcinoma↗

[High time to make choice: preventive or curative appendectomy?].

The authors advocate prophylactic appendectomy in conditions of wide application of laparoscopic surgery, refer to literature data on the absence of life-important functions in appendix and any functional disturbances after appendectomy. Taking into account high rate of development and difficulties in the diagnosis of acute appendicitis, favourable clinical and economical results of laparoscopic appendectomy, the authors suggest wider use of preventive removal of the appendix, especially in definite groups of population.

Appendectomy↗

CancerTrialMatch: a computational resource for the management of biomarker-based clinical trials at a community cancer center.

MOTIVATION: The widespread implementation of next-generation sequencing in cancer care has enabled routine use of molecular and biomarker profiling. At our cancer center, as with many others, biomarker-based clinical trials are increasingly available to oncologists as potential treatment options via molecular tumor boards. To better support this effort, we developed CancerTrialMatch, a systematic approach to capture structured clinical trial data and match patients to trials based on their disease characteristics and sequencing profiles. RESULTS: CancerTrialMatch is an open-source application designed to streamline clinical trial curation and patient trial matching, while also enabling an institution's curated trial portfolio to be distributed across the institution for easy access to providers, care teams and researchers. It facilitates curating, updating, and searching for trials through a semi-automated interface built using R Shiny, MongoDB, and Docker. While much of the trial data is retrieved via the clinicaltrials.gov Application Programming Interface, certain items like biomarkers and disease subtypes are entered manually. The user inputs disease type using the OncoTree classification, and provides relevant biomarker details, such as mutations, copy numbers, fusions, and other disease-specific markers. This resource reduces the time required for institutional trial management and helps to identify potential clinical trials for patients, ultimately supporting larger clinical trial enrollment and enhancing the clinical application of precision oncology. AVAILABILITY AND IMPLEMENTATION: CancerTrialMatch was implemented and tested on Windows 11 (64-bit, 32 GB RAM) using WSL2 with Ubuntu 22.04. Docker 27.0.3 and Docker Compose 2.28.1 were used to build images and containers. Users can build it by cloning the repo and following the README instructions and supplemental file (cancertrialmatchsupplemental.pdf) . The source code and example data are available in GitHub and Figshare at https://github.com/AveraSD/CancerTrialMatch and 10.6084/m9.figshare.28447367 respectively.

Humans↗

Local recurrence after curative resection for rectal cancer is associated with anterior position of the tumour.

BACKGROUND: Mobilization of rectal cancer can be difficult if the tumour is located anteriorly and may result in a higher incidence of local recurrence. The aim of this study was to determine whether local recurrence and survival following curative resection of rectal cancer were associated with the position of the tumour. METHODS: Data were drawn from a comprehensive, prospective hospital registry of all resections for rectal cancer from January 1990 to December 1998, with follow-up to December 2003. RESULTS: The 5-year local recurrence rate was 15.9 (95 per cent confidence interval (c.i.) 11.0 to 22.8) per cent in 176 patients with tumours that had an anterior component compared with 5.8 (95 per cent c.i. 2.8 to 11.9) per cent in 132 patients with tumours without an anterior component (P = 0.009). This association persisted after adjustment for other factors linked to local recurrence (hazard ratio (HR) 2.4 (95 per cent c.i. 1.1 to 5.4)). Similarly, anterior position had a significant negative independent association with survival (HR 1.4 (95 per cent c.i. 1.0 to 2.00)). CONCLUSION: Anterior position is an independent negative prognostic factor for both local recurrence and survival after curative resection of rectal cancer.

Adult↗

Incomplete excision of basal cell carcinomas: a retrospective audit.

BACKGROUND: The reported rates of incomplete excision of basal cell carcinoma (BCC) vary widely (5-25%) among centres around the world. Incomplete excision of skin malignancy is one of the 57 clinical indicators developed by the Royal Australasian College of Surgeons and the Australian Council on Healthcare Standards to act as a measure of the standard of surgical care. The study aims to determine the rate of incomplete excision of BCC at a major cancer centre. METHODS: Computerized data and patients' records were reviewed. From January 1997 to June 2000, a total of 3558 BCC were surgically excised with curative intent, of which 223 were reported to have been removed incompletely. RESULTS: The overall rate of incomplete excision was 6.3%. CONCLUSIONS: Given the limitations of a retrospective audit and reliability of the data, this result nevertheless compares favourably with reported figures in the literature.

Adult↗

[Research and surgical treatment of epilepsy].

The currently available surgical procedures for the treatment of epilepsy, from fundamental data to therapeutic results, including various means of investigation are reported. The work is based on a review of the literature and on the cases studied by the two teams from the Universities of Montreal and Bordeaux who share the same concept of epilepsy surgery. The patient groups of the two teams include 316 S.E.E.G., 214 cortectomies, 39 callosotomies and 2 multiple sub-pial transsections. In the first part, the authors attempt to demonstrate that the epileptic focus corresponds to the region where the seizures arise, that this focus is not directly comparable to the region where inter-ictal spikes are recorded and sometimes becomes autonomous from the causal lesion. The epileptic phenomenon has a definite harmful effect on cerebral functions and a probable self-aggravating potential. The second chapter summarizes the clinical data on which the indications and contraindications are based. These obviously depend on whether the intervention is intended to be curative or palliative. Various non-invasive and invasive investigations are then reviewed, according to their relative importance and the experience of each team. The main points developed are: the electroclinical correlations during seizures, the symptomatological data for differentiating between temporal and frontal lobe seizures, the contribution of M.R.I. in demonstrating the epileptogenic and epileptic lesions, the electrophysiological information suggesting that S.E.E.G. remains the most informative mean of investigation. The various methods of investigation of assessing electrical, functional (cerebral blood flow, metabolism) and morphological aspects of epilepsy, supply non-redondant findings about the localisation of the epileptic focus. The chapter on surgical techniques mainly discusses the various modes of implantation of subdural and intracerebral electrodes and reports the same rate of morbidity in both cases. Orthogonal teleradiography is still perfectly suited to the implantation of intracerebral electrodes. S.E.E.G. is still the most anatomically precise technique. However, in certain conditions, extraoperative E.Co.G. is more adequate. New surgical modalities have recently appeared such as the multiple subpial transsections which allow treatment of epileptic foci unapproachable by cortectomy and such as modified techniques of hemispherectomy, which by decreasing morbidity, renew interest in them. In the chapter on surgical results, the authors emphasize the methodological problems of evaluation that partly account for their wide variability. The results obtained with the various surgical modalities are reviewed. The outcome in cortectomies is discussed at length in terms of the data from the literature as well as the results reported by both teams.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

RegulonDB (version 5.0): Escherichia coli K-12 transcriptional regulatory network, operon organization, and growth conditions.

RegulonDB is the internationally recognized reference database of Escherichia coli K-12 offering curated knowledge of the regulatory network and operon organization. It is currently the largest electronically-encoded database of the regulatory network of any free-living organism. We present here the recently launched RegulonDB version 5.0 radically different in content, interface design and capabilities. Continuous curation of original scientific literature provides the evidence behind every single object and feature. This knowledge is complemented with comprehensive computational predictions across the complete genome. Literature-based and predicted data are clearly distinguished in the database. Starting with this version, RegulonDB public releases are synchronized with those of EcoCyc since our curation supports both databases. The complex biology of regulation is simplified in a navigation scheme based on three major streams: genes, operons and regulons. Regulatory knowledge is directly available in every navigation step. Displays combine graphic and textual information and are organized allowing different levels of detail and biological context. This knowledge is the backbone of an integrated system for the graphic display of the network, graphic and tabular microarray comparisons with curated and predicted objects, as well as predictions across bacterial genomes, and predicted networks of functionally related gene products. Access RegulonDB at http://regulondb.ccg.unam.mx.

Databases, Genetic↗

Local recurrence after curative resection of cancer of the rectum without total mesorectal excision.

PURPOSE: The aim of this article was to examine local recurrence after curative resection for carcinoma of the rectum in which the surgical technique of total mesorectal excision was not performed. METHODS: A single surgeon managed the patients and the data collected prospectively. Total excision of the distal mesorectum was not performed in the upper third or mid rectum. RESULTS: From 1969 to 1993 curative resections were performed in 549 patients, of which 17 died postoperatively, leaving 532 for analysis. Sphincter-saving resection was performed in 468 patients (88 percent) and abdominoperineal excision in 58 (10.9 percent). The pathology stages (Dukes) were A, 158 (29.7 percent); B, 184 (34.7 percent); and C, 190 (35.7 percent). Five hundred seventeen patients (97.2 percent) were followed up for a minimum of five years. The median period of follow-up was 82 months. Local recurrence confined to the pelvis occurred in 17 patients, and local recurrence associated with distant metastases occurred in 24 patients. The total five-year local recurrence rate was 7.6 percent. Local recurrence was increased in Stage C tumors (P = <0.0001). Diathermy dissection in the pelvis was associated with a decreased local recurrence rate (P = 0.023). The five-year survival rate in curative resections was 72.5 percent. CONCLUSIONS: It is essential that articles presenting local recurrence rates should include both local recurrence in isolation and that which occurs with distant metastases. Although total mesorectal excision for rectal cancer was not performed in this study, the local recurrence rate is not materially different from that in several articles where total mesorectal excision has been used. Whether the distal mesorectum needs to be pursued in mid-rectal cancer is not yet proven.

Adult↗

Prediction of recurrence after curative resection of gastric carcinoma invading the muscularis propria: a multivariate analysis.

BACKGROUND: In Japan, the incidence of gastric cancer invading the muscularis propria is about 10% of all patients with gastric cancer undergoing surgical resection. Although many prognostic factors for early gastric cancer and advanced gastric cancer have been identified, there are few reports concerning prognostic factors for gastric cancer invading the muscularis propria, and the characteristics of recurrence are not well understood.METHODS: We retrospectively analyzed data on 167 patients with gastric cancer that had invaded the muscularis propria. All patients had undergone curative resection.RESULTS: Recurrences were evident in 37 patients (22.2%). Based on our univariate analysis, the recurrence was associated with lymph node metastases. Multivariate analysis showed that independent risk factors for recurrence were lymph node metastases and location of tumor in the upper or lower one-third of the stomach. With respect to the pattern of recurrence, 17 (46.0%) were secondary to hematogenous recurrence, 8 (21.6%) to peritoneal dissemination, and 6 (16.2%) to a local recurrence in the remnant stomach and in regional lymph nodes. Most deaths occurred during the second year after surgery, and approximately two-thirds of all patients (64.8%) died within 3 years after surgery.CONCLUSION: In patients with the risk factors of lymph node metastases and tumor in the upper or lower one-third of the stomach, lymph node dissection and postoperative adjuvant therapy are vital to try to prevent recurrences, especially during the first 2 years after surgery.

Journal Article↗

Practice patterns and clinical guidelines for posttreatment follow-up of head and neck cancers: a comparison of 2 professional societies.

OBJECTIVES: To determine and compare the current follow-up practice patterns of members of 2 professional societies of head and neck surgeons, and to compare these with the societies' published clinical practice guidelines. DESIGN: A survey was mailed to the 640 members of the American Society for Head and Neck Surgery (ASHNS); results were compared with those of a similar survey of the 824 members of the Society of Head and Neck Surgery (SHNS) and with the clinical practice guidelines of the consensus committee of both societies. MAIN OUTCOME MEASURES: Data were collected regarding the frequency of follow-up visits after potentially curative resection of head and neck epidermoid carcinoma and the types of diagnostic studies performed at each visit. RESULTS: A total of 318 ASHNS members responded to 1 of the mailings (49.7%), of which 280 responses (43.8%) were evaluable. Most surgeons relied on directed history, physical examination, and routine chest radiograph at varying intervals for detection of recurrences and second primary tumors. Other tests were used sporadically. For frequency of follow-up testing, the percentage of surgeons who followed the published guidelines varied from 97% in postoperative year 1 to 62% in postoperative year 5. A mean of 24% of surgeons varied from the guidelines in their use of chest radiographs, and 45% varied in their use of liver function tests. The ASHNS members used significantly more office visits than the SHNS members during the first 2 postoperative years. CONCLUSIONS: The strategies used by members of the ASHNS and the SHNS for posttreatment surveillance after potentially curative resection of malignant neoplasms of the head and neck were generally similar but showed some important differences. Most surgeons used directed history and physical examination at regular intervals, and annual chest radiographs. The follow-up practices of most members of these societies, which have recently merged, fall within the recommendations of the Clinical Guidelines Task Force.

Adult↗

The impact of laparoscopy and laparoscopic ultrasonography on the management of pancreatic cancer.

HYPOTHESIS: Laparoscopy and laparoscopic ultrasonographic (LAPUS) examinations combined with a biopsy of the pancreatic lesion contribute significantly in the determination of resectability of pancreatic cancer. DESIGN: A prospective evaluation of the impact of laparoscopy and LAPUS on surgical decision making in patients with pancreatic cancer. SETTING: A general community hospital; the department of surgery serves as referral for pancreatic surgery. PATIENTS: During a 36-month period, 94 patients with pancreatic lesions were prospectively examined. Twenty-seven patients were found to have advanced disease. The remaining 67 patients were examined by laparoscopy and LAPUS to determine the resectability of the pancreatic tumor. RESULTS: Laparoscopy and LAPUS contributed new, additional data in 40 patients (60%). Advanced disease was found in 30 patients, precluding curative resection. The study indicated potentially resectable tumors in 37 patients (55%), including 3 defined by conventional imaging studies as probably unresectable, and these patients were operated on with the intention of curative resection. Thirty-three patients underwent resection, and 4 (6%) were found to have nonresectable disease and form the false-positive group of the study. A summary of the results shows that the study resulted in a change of the decision regarding surgical intervention in 24 patients (36%) and avoided unnecessary laparotomies in 21 (31%). The study had a sensitivity of 100%, a specificity of 88%, and a false-positive rate of 6%. The positive predictive value of the study is 89%, and the negative predictive value is 100%. CONCLUSIONS: Although rather invasive procedures that require general anesthesia and hospitalization, laparoscopy and LAPUS significantly contribute to the staging of patients with potentially resectable pancreatic cancer, avoiding unnecessary explorative laparotomies. These procedures should be performed in all patients with potentially resectable pancreatic cancer before explorative laparotomy.

Female↗

Transforming growth factor-beta1 enhances the lethal effects of DNA-damaging agents in a human lung-cancer cell line.

In tissue culture conditions, exogeneous active transforming growth factor-beta1 (TGF-beta1) enhances the lethal effect of DNA-damaging agents (UV-C, gamma rays, cisplatin, methotrexate and 5-fluorouracil) toward human A549 cells and mink Mv1Lu cells, as detected by the loss of their capacity to give rise to colonies; both these cell lines harbor a wild-type p53, as determined by immunoprecipitation. Contrastingly, the sole effect of the cytokine used alone is to inhibit reversibly the multiplication of the same cells without further impairing, once withdrawn from their environment, their capacity to divide and give rise to colonies. The lethal synergy between TGF-beta1 and UV-C was studied on mink and human cell lines, and the biomodulation by TGF-beta1 of cell killing by cisplatin, gamma rays, 5-fluorouracil or methotrexate was tested only on human cells. As investigated with UV-C-irradiated human A549 cells, TGF-beta1 appears to enhance apoptosis rather than to disturb the repair of DNA photolesions (mainly pyrimidine dimers) by the nucleotidic excision repair pathway according to results of nucleosomal ladder and comet tests. Our data raise the possibility that, in vivo, TGF-beta1 might affect the curative and/or undesirable secondary side effects of cancer therapy.

Animals↗

Prognosis of node-positive colon cancer.

The most recent American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system subgroups patients into one to three and four or more positive nodes. However, the Gastrointestinal Study Group and the National Surgical Adjuvant Breast and Bowel Project divides node-positive patients into one to four and five or greater. A Cox multi-variate retrospective analysis was done of the overall survival of node-positive colon cancer patients with the specific objective of determining the most appropriate subcategorization. Data on 306 patients with node-positive colon cancer who underwent potentially curative surgery from 1970 to 1984 were analyzed retrospectively. No patient received adjuvant chemotherapy. Also excluded were patients with synchronous resected metastatic disease or those with rectal primaries. The median follow-up was 6 years, and the median survival for the entire group was 8.6 years. By univariate analysis, the following were significant prognostic features: number of positive nodes (P less than 0.0001), degree of differentiation (P less than 0.0001), colon primary site (P = 0.009), tumor stage (P = 0.001), and tumor size (P less than 0.0001). Lymphatic/blood vessel invasion and a mucinous histology were not significant. By Cox multivariate analysis the number of positive lymph nodes remained the best discriminant of survival (P = 0.0001). The number of positive nodes was related inversely to prognosis with the optimal dichotomization between one to three (66% 5-year survival) and four or greater nodes (37% 5-year survival).

Colonic Neoplasms↗

Role of radiation therapy in patients with a diagnosis of both systemic lupus erythematosus and cancer.

OBJECTIVE: To determine whether radiation therapy (RT) is denied to patients with lupus and cancer and whether RT causes unusual toxicity in those receiving it. METHODS: We included patients with lupus followed at the University of Toronto Lupus Clinic between 1972 and 2001 who had developed cancer. Demographic, clinical, and laboratory information were collected prospectively. Pathologic proof of cancer was obtained. Three radiation oncologists blinded for the diagnosis of lupus, the modalities of cancer treatment, and the hypothesis of the study reviewed patient data independently. They assessed the indication for RT and whether it should be curative or symptomatic. Recommendation for RT was considered when at least 2 of the 3 radiation oncologists concurred. A review of the literature was conducted. RESULTS: Forty cases of cancer in 38 patients were identified. Most frequent cancer sites were breast (8), skin (8), digestive (7), and hematologic (7). Median patient age was 58 years. The radiation oncologists recommended RT in 26 cases, either with a curative (14) or a symptomatic intent (12). Only 4 patients received RT, 3 with a curative intent and 1 with a symptomatic intent. None of these 4 patients developed any unusual toxicity. The literature review did not support the fact that lupus patients do not tolerate RT. CONCLUSION: Sixty-five percent of our lupus patients with cancer could have received curative or symptomatic RT but only 10% received it. No patient developed any toxicity. RT may be inappropriately withheld from lupus patients with cancer.

Adult↗