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PubMed1989

Lung metastases after curative or noncurative irradiation of microscopic primary melanomas.

Melanomas growing in the feet of syngeneic C57BL/6 mice were treated with a single dose of X-irradiation. After doses of 0, 3.75, 7.5, 10, 20, or 30 Gy the tumor-bearing limb was amputated at tumor sizes 1, 2, 3, 4, or 5 mm. After doses of 40, 50, 62.5, or 72.5 Gy, progressive tumor growth did not occur, and amputation of tumor-bearing limbs was done when controls were 1, 2, 3, 4, or 5 mm in size. Eighteen days after amputation the mice were killed, and pulmonary metastases were documented at autopsy. None of the mice developed pulmonary metastases after curative irradiation of the primary foot tumor. After subcurative irradiation there was a significant increase (P less than .003) in pulmonary metastases. The size of the primary melanoma is important in the prediction of these metastases. In this model melanomas can be cured by an adequate dose of irradiation, but in those not cured the incidence of lung metastases is increased. The impact of this biologic phenomenon on survival is unclear.

Animals↗

PubMed1989

Local recurrence after curative resection of rectal cancer: a comparison of low anterior resection and abdominoperineal resection.

Local recurrence rates after either low anterior resection or abdominoperineal resection were compared in 109 patients undergoing curative surgery for adenocarcinoma of the rectum between 1979 and 1984. Follow-up information was available for 99 patients (91%). The overall recurrence rate was 19%; ten recurrences (26.3%) for low anterior resections and nine (14.7%) for abdominoperineal resections. (P less than .08). Recurrences were confirmed by biopsy or at reoperation. No significant difference in size of the lesion was evident at initial resection (average largest dimension 4.8 cm for low anterior and 5.5 cm for abdominoperineal resection). The average time to recurrence after resection was 18 months (16.5 months in the low anterior group vs. 19 months in the abdominoperineal group). Mean survival after recurrence was shorter for the abdominoperineal (3.4 months) as compared to the low anterior group (9.5 months) (P = .10). The overall median survival was 21 months (range 0-75 months) in both groups, and 38 patients were alive. Risk factors for recurrence were Dukes C lesions in patients who had a low anterior resection (8/18 or 44% recurrence) and poor histologic differentiation in patients who had either operation (3/6 or 50% recurrence).

Adenocarcinoma↗

PubMed1991

Local recurrence after curative resection for colorectal cancer: frequency, risk factors and treatment.

Analysis of 498 patients with colorectal carcinoma was retrospectively reviewed to evaluate the incidence, risk factors and therapy of local recurrent carcinoma following curative resection. Complete follow-up information was obtained in all but four patients (99.2%). After a median follow up of 42 months, 64 out of 469 (13.6%) patients developed local recurrence (LR). The incidence of LR was higher in rectal than in colon cancer patients (18.3% vs 8.9%) (P less than 0.005). Separate univariate and Cox analyses for rectal patients showed tumor site (P less than 0.02). Dukes stage (P less than 0.002), and adjuvant radiotherapy (P = 0.05) determined risk of LR. For colon cancer patients risk of LR was determined by histological tumor grade (P less than 0.01). Out of 64 patients, 5 (7.8%) underwent radical excision of LR. Forty percent of these survived at 5-year (P less than 0.08). Palliative treatment (radio-chemotherapy) obtained a 5-year survival of 15.3%, with no survivors in no-treatment group. These results suggest that local recurrent colorectal carcinoma remain a difficult treatment problem. More effective combinations of surgery and adjuvant therapy are therefore mandatory to reduce the incidence of local failure in high risk colorectal patients.

Adenocarcinoma↗

PubMed2005

Preclinical experiment of auxiliary partial orthotopic liver transplantation as a curative treatment for hemophilia.

The cause of hemophilia is deficiency of coagulation factor VIII production in the liver, which can be cured by liver transplantation. Because the hepatic function of hemophilia patients is quite normal except for production of factor VIII, auxiliary partial orthotopic liver transplantation (APOLT) is beneficial in that patient survival is secured by preserving native liver even in the event of graft loss. However, it is not known whether the graft of APOLT would be enough to cure hemophilia. We evaluated the efficacy and feasibility of APOLT for hemophilia in a canine hemophilia A model that we established. Partial left liver graft was taken from the normal donor (blood factor VIII activity > 60%). The graft was transplanted to the hemophilia beagle dog (blood factor VIII activity < 5%) after resection of the left lobe preserving native right lobe. Changes in time of blood factor VIII activity and liver function parameters were observed after APOLT. APOLT and perioperative hemostatic management were successfully performed. The blood factor VIII activity increased to 30% after APOLT, and was sustained at least 6 weeks throughout the observation period without symptoms of bleeding. The result demonstrated sustained production of factor VIII in the hemophilia recipient after APOLT. Transplantation of approximately one third of whole liver resulted in cure of hemophilia. In conclusion, it is suggested that APOLT would be feasible as a curative treatment of hemophilia A to improve quality of life of the patients.

Animals↗

PubMed2002

High numbers of granzyme B/CD8-positive tumour-infiltrating lymphocytes in nasopharyngeal carcinoma biopsies predict rapid fatal outcome in patients treated with curative intent.

This study determined whether tumour-infiltrating lymphocytes (TILs) in nasopharyngeal carcinomas (NPCs) include activated cytotoxic T lymphocytes (CTLs) and whether the numbers of activated CTLs in these biopsies are related to clinical outcome. Moreover, the study investigated whether the numbers of activated CTLs are associated with the expression of MHC class I proteins and the granzyme B antagonist PI-9 in the tumour cells. Forty-three Indonesian NPC patients (T(1-3), N(1-3), M(0)), who were treated with curative intent by radiotherapy only, were studied. Tumour-infiltrating activated CTLs were detected using antibodies against granzyme B, CD8, and CD56. Expression of MHC class I proteins and PI-9 was also determined by immunohistochemistry. Granzyme B-positive TILs were detected in all NPC biopsies. The presence of a high percentage (>25%) of granzyme B-positive TILs appeared to be a very strong predictor of a rapid fatal clinical outcome, independent of stage. Complete absence of MHC class I heavy chain expression in tumour cells was observed in 11 of 31 evaluable cases and low levels were observed in seven additional cases. No association between MHC class I expression and the numbers of granzyme B-positive TILs was observed. Expression of the granzyme B antagonist PI-9 in tumour cells was detected in three cases. It is concluded that the presence of many granzyme B-positive TILs in a selected group of Indonesian NPC patients is a strong and stage-independent marker for a rapid fatal clinical outcome.

Adult↗

PubMed2004

Fine-tuning the prediction of sequences cleaved by signal peptidase II: a curated set of proven and predicted lipoproteins of Escherichia coli K-12.

A curated set of 81 proven and 44 predicted lipoproteins of Escherichia coli K-12 was defined with the combined use of a literature survey, a variety of predictive tools and human expertise. The well-documented Gram-negative proteome of E. coli K-12 was chosen to assess how the different approaches complement each other and to ensure a stable definition of a consistent set of lipoproteins. The results of detailed analysis of such proteins at the level of a single proteome are presented, corroborated and rationalized.

Amino Acid Motifs↗

PubMed2004

Identifying and predicting behaviour outcomes in cancer patients undergoing curative treatment.

A lot of emphasis is now being placed in early identification of 'distress', a state that lies between the feelings of sadness and apprehension, and clinically defined syndromes. It is assumed that an intervention at this stage will check the progression along the continuum in cancer patients. We have been working in global distress in cancer patients undergoing multimodality treatment with curative intent, for over 5 years. It all started with the generation of a hypothesis which led to the development of the 'Distress Inventory for Cancer', its refinement, and finally to modelling distress. This article gives a brief overview of our work on distress as conceptualised by the National Comprehensive Cancer Network in 1998, adopted and modified by us using informal patient interviews, expert Delphi exercise and structured patient interviews.

Humans↗

PubMed2005

Application of InChI to curate, index, and query 3-D structures.

The HIV structural database (HIVSDB) is a comprehensive collection of the structures of HIV protease, both of unliganded enzyme and of its inhibitor complexes. It contains abstracts and crystallographic data such as inhibitor and protein coordinates for 248 data sets, of which only 141 are from the Protein Data Bank (PDB). Efficient annotation, indexing, and querying of the inhibitor data is crucial for their effective use for technological and industrial applications. The application of IUPAC International Chemical Identifier (InChI) to index, curate, and query inhibitor structures HIVSDB is described.

Abstracting and Indexing↗

PubMed2002

How surgeon age affects surveillance strategies for extremity soft tissue sarcoma patients after potentially curative treatment.

BACKGROUND: The optimal strategy for follow-up of extremity soft tissue sarcoma patients after potentially curative treatment remains unknown. We investigated whether the date of completion of formal surgical training affects choice of surveillance strategy. MATERIALS AND METHODS: The 1,592 members of the Society of Surgical Oncology were asked how often they use 12 separate surveillance modalities during years 1-5 and 10 postsurgery. The motivation underlying follow-up was assessed separately. Repeated-measures analysis of variance was used to compare practice patterns by the year in which the surgeon's formal surgery training was completed, controlling for tumor grade, tumor size, and year postsurgery. RESULTS: Of the 716 respondents, 318 performed surgery and also provided long-term postoperative surveillance for their patients. These respondents were considered evaluable. Erythrocyte sedimentation rate, extremity X ray, and bone scan were the follow-up tests which differed significantly among physician age groups. Surgeons who completed training more than 30 years ago ordered erythrocyte sedimentation rate more frequently (P < 0.001). Surgeons in the 21-30 year category ordered extremity X ray and bone scan more frequently (P < 0.05), but the absolute differences among age groups were quite small. Older surgeons were also significantly more likely to believe that follow-up is clinically worthwhile. CONCLUSIONS: The posttreatment surveillance practice patterns of the members of the Society of Surgical Oncology caring for extremity soft tissue sarcoma patients vary only marginally with the length of time since completion of training. Postgraduate education may be one factor homogenizing surgeon behavior in this important aspect of cancer patient care.

Aging↗

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↗

PubMed1996

Curative chemotherapy for acute myeloid leukemia: the development of high-dose ara-C from the laboratory to bedside.

In the bench to bedside development of drugs to treat patients with cancer, the common guide to dose and schedule selection is toxicity to normal organs patterned after the preclinical profile of the drug. An understanding of the cellular pharmacology of the drug and specifically the cellular targets linked to the drug's effect is of substantial value in assisting the clinical investigator in selecting the proper dose and schedule of drug administration. The clinical development of ara-C for the treatment of acute myeloid leukemia (AML) provides a useful paradigm for the study of this process. An understanding of the cellular pharmacology, cytokinetics and pharmacokinetics of ara-C in leukemic mice showed substantial schedule-dependency. Exposure to high doses for a short duration (C x t) resulted in a palliative therapeutic outcome. In marked contrast, exposure to lower doses for a protracted period (c x T) was curative. Clinical use of ara-C in patients with AML patterned after the murine experience, c x T approach, has been of limited benefit in terms of long-term disease-free survival. Studies with human leukemia blasts from patients have shown that for the majority of patients, the initial rate-limiting step is membrane transport, the characteristics of which are substantially affected by extracellular drug concentration (dose). This pharmacologic impediment is eliminated with the blood levels attained during the infusion of gram doses (1-3 gm/m2) of the drug (high-dose ara-C, HiDaC) for shorter periods of time, a C x t approach. Clinical confirmation of these pharmacologic observations is evident in the therapeutic efficacy of HiDaC in patients with relapsed or SDaC-refractory acute leukemia. This is further emphasized by the significantly improved leukemia-free survival of patients with AML treated with HiDaC intensification during remission compared to those patients treated with milligram doses typical of SDaC protocols. Thus, the identification and monitoring of important parameters of drug action in tumors during the course of a clinical trial can be of substantial assistance in optimizing drug dose and schedule so as to attain the best therapeutic index.

Acute Disease↗

PubMedDate not supplied

Curative surgery for gastric cancer: study of 166 consecutive patients.

From January 1980 to December 1991 we operated on 295 patients with a gastric carcinoma. In 166 cases (56.3%) surgery was performed with curative intent. In 93 patients (56%) a subtotal gastrectomy was performed, and in 73 cases (44%) a total gastrectomy. In all the cases a D-2 type lymphadenectomy was used. The global morbidity rate was 23%, and in-hospital mortality was 3.6%. The morbidity and mortality rates of these two operations were statistically different. Global 5-year survival estimate for the whole series is 61.3%. Univariate and multivariate analysis according to T and N (TNM classification), the number of positive nodes resected, and the relation of positive per resected nodes, revealed statistically different outcomes. This kind of quantitative classification allowed identification of high risk groups irrespective of site of nodal involvement. Tumors classified as intestinal or diffuse type by the Lauren classification had similar survival curves and 5-year survival estimates (p = 0.834). By univariate and multivariate analysis this classification did not reveal a prognostic value in this group of patients. In our opinion, tumor penetration and lymph node involvement are at present the most reliable prognostic factors available.

Adult↗

PubMed1992

Low anterior resection versus abdominoperineal excision: a comparison of local recurrence after curative surgery for "very low" rectal cancer.

In the controversy regarding whether sphincter-saving resection (SSR) or abdominoperineal resection (APER) is more appropriate for the treatment of very low rectal cancer, local recurrence rates seem to play a fundamental role in patient outcome. In order to operate an effective patient selection, very low rectal cancer is defined herein as being located within 4.5 to 7.5 cm from the anal verge. This retrospective report investigates the incidence of local recurrence after curative surgery for very low rectal carcinoma in 24 consecutive patients treated by the same surgical team over a 15-year period using the above surgical procedures. In the APER group, the local recurrence rate was 45.5%, occurring in 5 of 11 cases; and in the SSR group 46.1%, occurring in 6 of 13 cases, with no significant difference between the two groups. Recurrence was found within one year of surgical treatment in all except one case. Despite the strict follow-up program, it was only possible to perform reoperation in two recurrent cases, both previously submitted to SSR and diagnosed by means of transanal ultrasonography and macrobiopsy. The high incidence of local recurrence in this series is explained by the advanced stage of disease in the majority of cases. Thus, as the choice between APER and SSR does not seem to affect the incidence of local recurrence, which is related more to tumor size, site, stage, and grading, preservation of the sphincters and restoration of digestive continuity should be achieved whenever technically possible.

Adenocarcinoma↗

PubMed1993

The unusual development of empyema with multiple alveolobronchiolar fistulae 8 years after non-curative resection and radiation for lung cancer: report of a case.

We present herein the case of a man who developed empyema with multiple lung fistulae 8 years after receiving postoperative radiation for a residual tumor on the bronchial stump. The patient was successfully managed with two-stage surgery, involving an open window thoracotomy, followed by omental flap transfer. This case documents how postoperative radiotherapy that was effective following non-curative resection was also responsible for the development of empyema. Furthermore, although the empyema was successfully treated using the omentum, a small free space remained in the thorax, which resolved within 2 months.

Aged↗

PubMed1995

Concomitant coronary bypass grafting and curative surgery for cancer.

The surgical management of patients with concomitant critical coronary artery disease (CAD) and surgically resectable cancer is controversial. We evaluated 19 patients who underwent concomitant coronary artery bypass grafting (CABG) and curative operation for cancer of the stomach in 9 patients, the colon in 4, the lung in 4, and the breast in 2. Each cancer operation was performed under stable hemodynamics without any serious bleeding tendency, immediately after CABG with an average of 2.5 +/- 0.8 grafts. There were no operative deaths and no incidences of perioperative myocardial infarction. Postoperative complications developed in three of the patients with lung cancer: respiratory dysfunction caused by phrenic nerve paralysis in two and mediastinitis in one. During the mean follow-up period of 33 +/- 23 months, 5 patients died of recurrent cancer or non-cardiac disease; however, all 19 patients remained free from any postoperative cardiac events and their quality of life apparently improved. This experience suggests that such simultaneous correction would be safe and beneficial in carefully selected patients who have surgically correctable CAD and potentially curable cancer.

Adult↗

PubMed1994

Curative local control of malignant tumors in the acetabulum by intraoperative radiotherapy.

As treatment for malignant tumors in the acetabular region of the pelvis, radiotherapy, mainly in the form of intraoperative radiotherapy (IORT), was carried out in four patients. One had a malignant fibrous histiocytoma of bone and three had metastatic tumors from the stomach and lung. Over follow-up period, ranging from 3 to 46 months, satisfactory limb function was preserved in three patients; the fourth suffered from femoral nerve palsy as a complication of IORT. Cessation of growth was observed radiologically in all the tumors, and curative local control was proven histologically in two patients at autopsy.

Acetabulum↗

PubMed1992

Postischemic breakdown in hippocampal protein synthesis and mnesic deficits in rats: pharmacological improvement by curative naftidrofuryl treatment.

This work was designed to investigate the effects of brain ischemia on mnesic retention in the model of unilateral microsphere embolization in rats. Using various radioactive tracers as well as a learning/memory test, we could correlate following parameters: regional blood flow, protein synthesis and memory retention. All were severely impaired by the hemispheric multi-infarction. A curative treatment with naftidrofuryl (15 mg/kg i.p.) for 3 consecutive days strongly improved the mnesic capacities of the animals, and this effect was corroborated by a marked protective drug action on protein synthesis in the hippocampus. Indeed, studies on valine incorporation into proteins revealed that, despite having no quantitative effect on regional blood flow, naftidrofuryl allowed an almost normal functioning of protein synthesis. As naftidrofuryl had also no direct effect on protein synthesis in the intact contralateral hemisphere, this effect was consequently attributed to the metabolic and/or antiserotoninergic effects of the drug.

Animals↗

PubMed1992

Prognosis of gastric carcinoma after curative surgery. A population-based study using multivariate crude and relative survival analysis.

A population-based series of 246 gastric cancer patients operated for cure and who survived the postoperative phase was reviewed to determine prognostic factors after potentially curative treatment. The overall five-year observed survival rate was 34.8%, and the relative survival rate was 43.9%. Previous history of gastric ulceration, tumor location, tumor size, gross appearance, extension within the gastric wall, and number of proximal lymph nodes involved were significantly related to both crude and relative survival rates. Age was a significant prognostic factor when considering crude survival rates, but it had no influence on relative survival rates. Multivariate analysis of crude and relative survival gave similar results except for age. The covariates retained in the final model were, by decreasing importance, extension within the gastric wall, lymph node involvement, gross appearance and tumor location. Combining the two major prognostic criteria, tumor extension through the gastric wall and lymph node involvement, four prognostic categories could be determined with five-year corrected survival rates ranging from 92% in patients with a carcinoma limited to the gastric wall to 17% in patients with more than two positive nodes whatever the extension in the gastric wall. Gross appearance had no influence on prognosis for carcinomas limited to the gastric wall, but had a significant impact on prognosis of more extended carcinomas. From these data, a simple staging system requiring only routinely available pathological data was proposed. This classification could be helpful for planning multicenter clinical trials on this disease where progress in therapy is needed.

Carcinoma↗