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At least 19 recordsLinked to original sources

PubMed1998

Regulation of mRNA localization by transmembrane signalling: local interaction of HB-GAM (heparin-binding growth-associated molecule) with the cell surface localizes beta-actin mRNA.

Localization of mRNAs is currently thought to be partially responsible for molecular sorting to specific compartments within the cell. In mammalian cells the best-studied example is the beta-actin mRNA that is localized to the cell processes, and its localization is necessary in migratory responses of cells. It is reasonable to assume that mRNA localization within cells is coupled to transmembrane signalling due to extracellular factors, but little is known about such putative mechanisms. We show here that HB-GAM, an extracellular matrix-associated factor that enhances migratory responses in cells, is able to localize beta-actin mRNA when locally applied to cells via microbeads. The HB-GAM-induced mRNA localization is specifically inhibited by low concentrations of heparin and by heparitinase treatment of cells, showing that cell-surface heparin-type glycans are required for the effect. The finding that soluble N-syndecan is also inhibitory suggests that the transmembrane proteoglycan N-syndecan, previously identified as an HB-GAM receptor, is involved in the mRNA-localizing effect of HB-GAM. Inhibition of the mRNA localization by the src-kinase inhibitor PP1 is compatible with an N-syndecan-mediated effect since the receptor function of N-syndecan has been recently found to depend on the src-kinase signalling pathway. The mRNA-localizing activity of N-syndecan is also suggested by the finding that affinity-purified anti-N-syndecan antibodies coated on microbeads are able to localize beta-actin mRNA.

Actins↗

PubMed1990

Isolated limb perfusion for localized melanoma of the extremity. A matched comparison of wide local excision with isolated limb perfusion and wide local excision alone.

The therapeutic efficacy of isolated limb perfusion in patients with localized melanoma of the extremity remains controversial. We compared patients treated at the University of Texas M.D. Anderson Cancer Center, Houston, with wide local excision and isolated limb perfusion using either melphalan or imidazole carboxamide with a group matched for prognostic factors from the University of Alabama at Birmingham and the University of Sydney (Australia) who were treated with wide local excision alone. No significant difference in disease-free or overall survival rates was found between patients treated with wide local excision with adjuvant isolated limb perfusion or wide local excision alone. However, a subset of patients with thicker lesions (greater than 2.0 mm) treated with wide local excision and isolated limb perfusion using melphalan had a significant improvement in both disease-free and overall survival rates. These data suggest that isolated limb perfusion using melphalan may improve survival rates in selected patients with localized melanoma of the extremity who are at increased risk for local and regional micrometastases, and justifies the continued study of this treatment approach in prospective clinical trials.

Aminoimidazole Carboxamide↗

PubMed1976

Decreases of local brain temperature due to convection (local brain blood flow) and increases of local brain temperature due to activity.

The influence of local brain blood flow upon variations of local brain temperature in chronical experiments was investigated in cats. It was found that changes of local brain temperature in chronic experiments are esclusively due to changes of local metabolic heat production as long as the temperature of brain inflowing blood remains constant. Decreases of temperature due to convection (increase of local blood flow) are smaller than increases of temperature due to activity.

Animals↗

PubMed1997

The sequential change of local cerebral blood flow and local cerebral glucose metabolism after focal cerebral ischaemia and reperfusion in rat and the effect of MK-801 on local cerebral glucose metabolism.

In order to investigate the time course change of local cerebral blood flow (1CBF) and local cerebral glucose metabolism (ICGM) and the effect of MK-801 (dizocilpine), an NMDA receptor antagonist on glucose metabolism in a middle cerebral artery occlusion-reperfusion model, 14C-Iodo-antipyrine and 14C-Deoxyglucose autoradiographic method have been used. The 1CBF was reduced to 0-10% of the control level in the ischaemic core and to 12-40% in the ischaemic penumbra between 60 and 120 min after the onset of the ischaemia. In the ischaemic core, the marked hyperfusion appeared at 15 min and maintained about 30 to 45 min following reperfusion. In the ischaemic penumbra, the hyperfusion during reperfusion was not found. Hypermetabolism occurred at 30 min and reached to the peak at 60 min after the middle cerebral artery (MCA) occlusion both in the ischaemic core and in the penumbra. The shift from hyper- to hypometabolism was observed during the ischaemia. The reperfusion following 2 hours of MCA occlusion facilitated the decrease of cerebral glucose metabolism in the ischaemic region. The pretreatment of MK-801 (0.4 mg/kg) inhibited both increased glucose metabolism during the ischaemia and decreased glucose metabolism during the reperfusion. The effect of limiting decreased glucose metabolism during the reperfusion by MK-801 was remarkable in the ischaemic penumbra. These findings support the hypothesis that excitation-induced hypermetabolism play a major role in the ischaemic insult following focal cerebral vascular occlusion.

Animals↗

PubMed1983

Local-regional treatment of patients with simultaneous local-regional recurrence and distant metastases following mastectomy.

High-dose, large volume local-regional irradiation has been shown to be necessary in patients with local-regional recurrence of breast cancer without coexisting distant metastases; however, no studies exist that deal with the dose and volume of local-regional irradiation required for patients with both local-regional recurrence and distant metastases. This report is an analysis of 68 patients who presented with previously untreated local-regional recurrence and coexisting distant metastases. Thirty-five of these patients were treated with local-regional irradiation and systemic therapy; the remaining 33 patients received systemic therapy only. An analysis of the dose and volume in the 35 irradiated patients showed that if the irradiation was inadequate (dose less than 4500 rad and volume not large enough to encompass the entire involved site), the incidence of uncontrolled local-regional disease for the duration of life was 79%, similar to the 64% rate of uncontrolled local-regional disease in the 33 patients not receiving local-regional irradiation. On the other hand, if the dose to the recurrence was at least 4500 rad and if the field was large enough to encompass the entire site containing the recurrence, the incidence of uncontrolled local-regional disease for the duration of life was only 27%. The present study also suggests that local-regional irradiation may be indicated in patients with asymptomatic as well as symptomatic local-regional disease. In patients with distant metastases and initially asymptomatic local-regional disease, adequate irradiation resulted in a lower incidence of ultimate local-regional symptoms when compared to similar patients who were treated with inadequate or no local-regional irradiation. This difference was not quite statistically significant because of the small number of patients in each group.

Breast Neoplasms↗

PubMed1999

Enhancement of local control in locally advanced node-positive nasopharyngeal carcinoma by adjunctive chemotherapy.

PURPOSE: To determine the efficacy of chemotherapy adjunctive to radical radiotherapy (neoadjuvant +/- adjuvant) in patients with node-positive nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: All the node-positive patients given adjunctive chemotherapy between 1984-1989 (n = 209, CHEMO) were compared with all the node-positive patients treated by radical radiotherapy alone during the same period (n = 409, NCHEMO). The CHEMO group had significantly more bulky nodes, lower cervical/supraclavicular nodes, and more advanced overall stages than the NCHEMO group because nodal size (> or =24 cm) was used as a selection criterion for chemotherapy (1984-1988 departmental protocol and 1988-1989 prospective randomized trial). The chemotherapy consisted of two courses of neoadjuvant cisplatin (100 mg/m2 D1) and 5-fluorouracil (5-FU) (1 gm/m2 D1-D3) in 191 patients. In addition to the two courses of neoadjuvant, four courses of adjuvant chemotherapy, of the same combination, were given after radical radiotherapy in a further 18 patients. Radical radiotherapy delivered a nasopharyngeal dose of 60-62.5 Gy. In addition, parapharyngeal booster external radiotherapy (20 Gy) was given in the presence of parapharyngeal involvement, and intracavitary brachytherapy (24 Gy) was used to treat any local residual tumor diagnosed at 4-6 weeks after external radiotherapy. Both crude and actuarial rates were compared (survival, distant metastases, and local failures) between CHEMO and NCHEMO for all patients, for individual Ho's overall stage, for patients with nodes of different sizes (< or =3 cm, >3-< or =6 cm, >6 cm), for individual T-stage and individual N-stage, and for patients belonging to different gender and different age groups (<40 years, > or =40 years). Multivariate analyses using the Cox Regression Model were performed to identify significant prognostic factors. RESULTS: With a median follow-up of 5.5 years (range 0.7 to 10 years), CHEMO had significantly less local failures overall than NCHEMO; this was especially true for patients with advanced stages (III + IV). Additionally, in all nodal-size subgroups, in all node-positive T3, and in node-positive T3-Stage IV, there was a significant reduction in local failures after chemotherapy. There was a trend toward fewer local failures in favor of chemotherapy in Stage III, Stage IV, and T3-Stage III (0.05<p< or =0.1). There was no difference in local failures between CHEMO and NCHEMO in Stage II or in T1 and T2. The multivariate analyses identified the administration of adjunctive chemotherapy to be of independent significance in determining the local failure rate for all patients, the T3 (node-positive), and the advanced overall stages (III and IV combined). There was no difference in overall survival, relapse-free survival, and distant metastasis rates between CHEMO and NCHEMO among patients belonging to Stages III and IV despite the presence of more advanced nodal diseases in CHEMO. There were very few late local relapses in patients given adjunctive chemotherapy, in contradistinction to the well-known predisposition of NPC to late local relapses after radical radiotherapy. CONCLUSION: Adjunctive chemotherapy enhanced local control in node-positive NPC in general, and node positive-T3 and -T3-Stage IV in particular with reduction of late local relapses. The enhancement in local control of the locally advanced NPC could be explained by the significant shrinkage of the primary tumor by the neoadjuvant chemotherapy, leading to an increased safety margin between the tumor volume and the radiation volume. We recommend that adjunctive chemotherapy (neoadjuvant +/- adjuvant) should become an integral part of the multimodality curative treatment for patients with node-positive T3 NPC.

Adolescent↗

PubMed1997

Two copies of a subelement from the Vg1 RNA localization sequence are sufficient to direct vegetal localization in Xenopus oocytes.

Localization of mRNA has emerged as a fundamental mechanism for generating polarity during development. In vertebrates, one example of this phenomenon is Vg1 RNA, which is localized to the vegetal cortex of Xenopus oocytes. Vegetal localization of Vg1 RNA is directed by a 340-nt sequence element contained within its 3' untranslated region. To investigate how such cis-acting elements function in the localization process, we have undertaken a detailed analysis of the precise sequence requirements for vegetal localization within the 340-nt localization element. We present evidence for considerable redundancy within the localization element and demonstrate that critical sequences lie at the ends of the element. Importantly, we show that a subelement from the 5' end of the Vg1 localization element is, when duplicated, sufficient to direct vegetal localization. We suggest that the Vg1 localization element is composed of smaller, redundant sequence motifs and identify one such 6-nt motif as essential for localization. These results allow insight into what constitutes an RNA localization signal and how RNA sequence elements may act in the localization process.

Animals↗

PubMed1989

Local reactivity, local resistance and systemic dissemination in Mycobacterium lepraemurium (MLM) infection.

Local reactivity measured as swelling of the infected footpad, local resistance to bacterial multiplication, and capacity to limit systemic dissemination were studied in C57BL, C3H/Bom, C3H/HeJ, and A/Sn mice inoculated with Mycobacterium lepraemurium. C57BL mice developed a strong local reaction with a sudden onset, and effectively limited local multiplication as well as systemic dissemination of bacteria to the liver and spleen as determined 19 weeks after the inoculation. C3H/Bom mice showed no local reaction, had high numbers of bacteria locally, and had extensive systemic dissemination of the infection. C3H/HeJ mice, on the other hand, developed a small local reaction and had less systemic dissemination of bacteria than C3H/Bom mice. In C57BL mice and in the two C3H substrains local reactivity, local resistance to infection, and resistance to systemic spread of the infection paralleled each other. In contrast, A/Sn mice showed a small local reaction, had the most extensive bacterial multiplication at the site of inoculation of the four mouse strains tested, and at the same time were the mice that most effectively restricted systemic dissemination of the infection. Thus, the mechanisms restricting local bacterial multiplication may be different from the mechanisms limiting bacterial dissemination. Neither bacterial growth locally at the site of subcutaneous inoculation in the footpad, nor systemic dissemination of the infection, followed a mouse strain pattern consistent with the Ity/Lsh/Bcg gene model. In experimental mycobacterial infection both local bacterial growth at the site of inoculation and systemic dissemination should be determined.

Animals↗

PubMed1988

[Local treatment of locally recurrent breast cancers].

For the treatment of recurrent breast cancer, surgical treatment of the local lesion is only of limited significance, leaving a major role for systemic treatment such as chemotherapy and endocrine therapy. Therefore, a new method of local treatment other than surgical removal alone, or systemic treatment of these locally recurrent breast cancers is required. For the treatment of locally recurrent breast cancer, intra-arterial infusion chemotherapy was performed through both the internal mammary artery and subclavian artery or individually. Fourteen cases of locally recurrent breast cancer in our hospital were treated with this therapy. Continuous infusion of 5-fluorouracil and intermittent injections of mitomycin, adriamycin or 4'-epi-adriamycin were jointly or individually done into each artery. Regression of the locally recurrent mass was periodically measured from 4 to 6 weeks after infusion. The percentage of patients with PR was 35.7%. Intra-arterial infusion chemotherapy is a useful preliminary procedure for systemic treatment of local lymph node recurrence from breast cancer. A treatment involving local infusion of the non-specific immuno-activators, OK-432 and PSK, has also been performed for local recurrent lesions of breast cancers. We injected OK-432 and 5% PSK solution into patients with locally recurrent breast cancers and studied their suppressive effect on tumor proliferation. Macroscopically, PR was noted in 3 of 12 patients given OK-432. CR+PR were obtained in 9 of 12 patients given PSK. These results suggest that local injection of OK-432 and PSK solution is beneficial in the management of nodular or scattered-type locally recurrent tumors except for infiltrating type.

Adult↗

PubMed1992

A report of RTOG 8206: a phase III study of whether the addition of single dose hemibody irradiation to standard fractionated local field irradiation is more effective than local field irradiation alone in the treatment of symptomatic osseous metastases.

Hemibody irradiation (HBI) in a single exposure is an effective and safe technique for palliation of symptoms due to widespread bony metastases (RTOG 78-10). The present study (82-06) sought to explore the possibility that HBI added to local-field irradiation might delay the onset of metastases in the hemibody effected, as assessed by bone scans and X rays, and decrease the frequency of further treatment. The results of this clinical trial establish that 800 cGy of HBI is indeed causes micro-metastases to regress, perhaps completely. A total of 499 patients were randomized to receive either HBI or no further treatment following completion of standard palliative local field irradiation (300 cGy x 10) to the symptomatic site. Improvement was seen in time-to-disease progression at one year, 35% for local + HBI versus 46% on the local-only control arm. Time-to-new disease in the targeted hemibody was also improved. At one year, 50% of patients on the local + HBI arm showed new disease compared to 68% on the local-only arm. Furthermore, the median time-to-new disease within the targeted HBI area was 12.6 months for the local + HBI arm versus 6.3 months for patients in the local-only arm. Time-to-new treatment within the hemibody segment was also delayed. At one year, 76% of the local only group had been retreated versus 60% in the local + HBI arm. There were no fatalities and no radiation pneumonitis was seen in the local + HBI arm. Overall, the incidence of toxicities was low (5-15%). The occurrence of severe hematopoetic toxicities were significantly different in the local + HBI arm, but they were transitory. One life-threatening thrombocytopenia occurred, for a limited time, indicating excellent tolerance to HBI. This clinical trial demonstrates that HBI has the potential to be used to treat systemic and occult metastases, particularly if both halves of the body can be treated.

Aged↗

PubMed1999

fatvg encodes a new localized RNA that uses a 25-nucleotide element (FVLE1) to localize to the vegetal cortex of Xenopus oocytes.

Vegetally localized transcripts have been implicated in a number of important biological functions, including cell fate determination and embryonic patterning. We have isolated a cDNA, fatvg, which encodes a localized maternal transcript that exhibits a localization pattern reminiscent of Vg1 mRNA. fatvg is the homologue of a mammalian gene expressed in adipose tissues. The fatvg transcript, unlike Vg1 which localizes strictly through the Late pathway, also associates with the mitochondrial cloud that is characteristic of the METRO or Early pathway. This suggests that fatvg mRNA may utilize both the METRO and Late pathways to localize to the vegetal cortex during oogenesis. We have dissected the cis-acting localization elements of fatvg mRNA and compared these elements with Vg1 mRNA. Our results indicate that, like most localized RNAs, in a variety of systems, transcripts of fatvg contain localization elements in the 3'UTR. The 3'UTR of fatvg mRNA contains multiple elements that are able to function independently; however, it functions most efficiently when all of the elements are present. We have defined a short 25-nucleotide element that can direct vegetal localization as a single copy. This element differs in sequence from previously described Vg1 localization elements, suggesting that different localization elements are involved in the localization of RNAs through the Late pathway.

3' Untranslated Regions↗

PubMed1992

The effect of systemic therapy on local-regional control in locally advanced breast cancer.

One hundred and seven patients with locally advanced breast cancer were prospectively referred for multimodality treatment on protocol using chemohormonal therapy to maximal response followed by local treatment and maintenance therapy. Forty-eight patients (45%) were diagnosed with Stage IIIA disease, 46 (43%) with Stage IIIB inflammatory cancer, and 13 (12%) with Stage IIIB non-inflammatory disease. Induction therapy consisted of cyclophosphamide, doxorubicin, methotrexate, and 5-fluorouracil with hormonal synchronization using tamoxifen and conjugated estrogens. Local treatment was determined by response to chemotherapy. Patients with a clinical parital response underwent mastectomy followed by local-regional radiotherapy while patients with a clinical complete response were biopsied for pathologic correlation. Those with residual disease received mastectomy followed by radiotherapy while those with a pathologic complete response received radiation only to the intact breast and regional nodes. With a median follow-up of 64 months, patients with IIIA disease had a significantly lower local-regional failure rate compared to IIIB inflammatory patients, with the 5-year actuarial local-regional failure rate as only site of first failure 3% for IIIA disease versus 21% for IIIB inflammatory cancer (p = .02), and local-regional failure as any component of first failure 12% versus 36% (p = .01), respectively. When local-regional failure was analyzed by repeat biopsy, 5/31 (16%) patients with a pathologic complete response treated with radiation only developed a local-regional failure versus 2/53 (4%) with residual disease treated with mastectomy and postoperative radiotherapy. The 5-year actuarial local-regional failure rate as first site of failure was 23% for radiation only versus 5% for mastectomy and post-operative radiotherapy (p = .07). The response to chemotherapy did not reliably predict local-regional control. Both relapse-free survival and overall survival were significantly better for IIIA versus IIIB patients; stratification by repeat biopsy did not however, significantly affect either relapse-free or overall survival.

Adult↗

PubMed1989

Neoadjuvant chemotherapy for localized Ewing's sarcoma of the extremities: preliminary results of a protocol which uses surgery (alone or followed by radiotherapy) for local control.

From June 1983 to December 1985, thirty-eight patients with localized Ewing's sarcoma of the extremities were treated with a protocol that consisted of an initial nine week period of polychemotherapy (vincristine, adriamycin and cyclophosphamide) followed by local therapy and additional chemotherapy (vincristine, adriamycin, cyclophosphamide and dactinomycin) for one year. As local treatment all patients were offered surgery; thirty-two accepted and six refused. These six patients were locally treated with radiotherapy alone (50 Gy). In the remaining patients an amputation was performed in one case and a resection in thirty-one. In resected patients when a wide margin was achieved (24 cases) no further local treatment was performed; when it was marginal (5 cases) or intralesional (2 cases) radiotherapy at lower doses (40 Gy) followed. At mean follow-up of thirty-seven months the percentage of continuously disease-free patients was 50% for those treated with radiotherapy, 76% with surgery, and 85% with surgery and radiotherapy. Eight patients developed metastatic disease and two patients had local recurrence and metastases. The local recurrences were seen in one patient locally treated with surgery and in one locally treated with radiotherapy. Nine major local complications were observed: three in patients treated with radiotherapy, five in patients treated with surgery, and one in a patient treated with surgery and radiotherapy. These results indicate that after induction chemotherapy conservative surgery is possible in almost all cases of Ewing's sarcoma of the extremities and that such treatment is better than radiotherapy alone as local therapy.

Adolescent↗

PubMed1992

Local administration of monoclonal antibody-drug conjugate: a new strategy to reduce the local recurrence of colorectal cancer.

This report investigates the application of monoclonal antibody A7 and its drug conjugate in locally controlling colorectal cancer. The experimental protocol consisted of local retention, lymphatic delivery, normal organ distribution, systemic toxicity, and tumoricidal effects. When 125I-labeled monoclonal antibody (Mab) A7 was injected into the pelvis and the thigh of Balb/c mice, a high local retention unrelated to antigen-antibody interaction was observed at the injected site for 24 h after injection. An analysis of local retension properties related to antigen-antibody interaction, conducted by intratumorally or peritumorally injecting 125I-Mab A7 into the tumor-bearing athymic nude mice, revealed a significantly higher tumor localization of Mab A7 in comparison to i.v. injection. 125I-Mab A7 accumulated to a great extent in the ipsilateral regional lymph node but not in the contralateral regional lymph node. Normal organ accumulation of Mab A7 was lower in the locally injected group than in the i.v. injected group. Intratumoral injection of Mab A7-neocarzinostatin (A7-NCS) led to the complete remission of established tumor in 5 of 6 antigen-positive xenograft-bearing mice but exhibited a complete remission in only 1 of 6 antigen-negative xenograft-bearing mice. A single local injection of A7-NCS inhibited tumor development in 12 of 16 and 5 of 15 antigen-positive tumor-bearing mice and antigen-negative tumor-bearing mice, respectively, whereas neither a systemic injection of A7-NCS and NCS nor a local injection of NCS and saline had a notable inhibitory effect on tumor development. Systemic toxicity of NCS was markedly reduced when it was locally administered in the antibody-conjugated form. These findings indicate that local injection of immunoconjugate is a promising new field for controlling the local recurrence of colorectal cancer.

Animals↗

PubMed2000

Exploring local and non-local interactions for protein stability by structural motif engineering.

In order to probe the relative contribution of local and non-local interactions to the thermodynamic stability of proteins, we have devised an experimental approach based on a combination of motif engineering and sequence shuffling. Candidate chain segments in an immunoglobulin V(L) domain were identified whose conformation is proposed to be dominated by non-local interactions. Locally interacting structural motifs of a different conformation were then constructed as replacements, by introducing motif consensus sequences. We find that all nine replacements we constructed systematically reduce the folding cooperativity. By comparing this destabilising effect with the folding transitions of shuffled sequences for three of these motifs, we estimate the contribution of local, native interactions to the free energy of folding. Our results suggest that local and non-local interactions contribute to stability by an approximately equal amount, but that local interactions stabilise by increasing the resistance to denaturation while non-local interactions increase folding cooperativity. The systematic loss of stability by sequence shuffling in these host-guest experiments suggests that the designed interactions indeed are present in the native state, thus consensus sequence engineering may be a useful tool in structure design, but non-local interactions must be taken into account for global stability engineering. Statistical approaches are powerful tools for engineering protein structure and stability, but an analysis based on local sequence propensities alone does not adequately represent the balance of sequence and context in protein structures.

Amino Acid Motifs↗

PubMed1994

Breast conservation therapy: local tumor control in patients with pathologically clear margins who receive 5000 cGy breast irradiation without local boost.

A retrospective study was performed to determine the value of pathological evaluation of inked primary tumor specimen margins in the local control of patients with stage I and II breast cancer. In 150 patients with 153 invasive breast cancers, treatment involved surgical resection of the primary tumor, pathological determination of tumor-free inked specimen margins, and 5000 cGy whole breast radiation therapy (RT) without tumor bed RT local boost. This approach yielded an actuarial five-year local control rate of 95%. The local control rate was 96% for T-1 cases and 93% for T-2 cases. The local control rate was 96% for patients with clear margins achieved at initial resection and 94% for patients with clear margins achieved at re-excision. Among patients with clear margins at re-excision, the local control rate was 97% for those with no residual cancer and 88% for those with residual cancer. Patients with surgical margins clear by 3 mm or less had a local control rate of 92% at five years. Local control rates appear to be comparable to other breast conservation approaches which routinely employ local RT boosts. In omitting the local RT boost in patients with clear margins, the overall RT course will be briefer and the cosmetic changes associated with high-dose, large volume local RT boosts can be avoided.

Breast Neoplasms↗

PubMed1994

Salvage surgery for locally advanced and locally recurrent breast cancer.

OBJECTIVE: To determine if local control of breast cancer can be regained in patients with locally advanced and recurrent tumors using aggressive surgical treatment and reconstruction. DESIGN: A retrospective review of 15 consecutive patients. Patients were followed up from 8 to 32 months. SETTING: A university tertiary care facility in a metropolitan area. PATIENTS: All patients with locally advanced or recurrent breast cancer without known metastatic disease who underwent radical surgical resection of locally advanced breast cancer with reconstruction. MAIN OUTCOME MEASURES: Primary outcome measures were pathological findings, type of surgery, length of hospital stay, complications, local recurrence, and survival. RESULTS: Pathological findings showed 12 adenocarcinomas (80%) and three sarcomas (20%). Thirteen patients (86.7%) had undergone previous surgery, 11 (73.3%) had undergone previous radiation therapy, and all adenocarcinomas were progressing while patients were receiving chemotherapy. Full-thickness chest wall resection that included bone was required in 46.7%. The average hospital stay was 11.5 days. While 10 patients (66.7%) eventually manifested metastatic disease, local recurrence developed in only one. Minor complications occurred in six patients (40%) and major complications occurred in three (20%). There were no perioperative deaths. CONCLUSIONS: Patients presenting to our service had locally aggressive tumors that were recalcitrant to maximal medical management. With radical surgical treatment and reconstruction, there were no deaths, significant morbidity was low, and all but one patient regained local control. We found that aggressive surgical treatment and reconstruction is not only feasible in patients with locally advanced breast cancer but may be the only hope for local control in these patients who are difficult to treat.

Adenocarcinoma↗

PubMed1987

Localized operable soft tissue sarcoma of the upper extremity. Presentation, management, and factors affecting local recurrence in 108 patients.

Radical ablative surgery for upper extremity sarcoma often results in significant loss of function. With the recent emphasis on limb preservation, function-sparing excision has been combined with adjuvant radiation and chemotherapy in an increasing number of patients. To assess the effect of changing management on local recurrence rates and identify factors governing local failure, the records of 108 patients with operable, nonmetastatic soft tissue sarcoma of the upper extremity, treated at the Memorial Sloan-Kettering Cancer Center between 1968 and 1978, were reviewed. Median follow-up care was 8.2 years. One third of the patients presented with locally recurrent tumors after initial treatment elsewhere. Over half of the lesions were above the elbow and 62% were high grade. Seventy-three patients (68%) had limb-sparing surgery (LSS), but margins were considered adequate in less than half. Local recurrence was directly related to the adequacy of the surgical margins and was significantly higher in the LSS patients (p = 0.008). Other factors associated with an increased risk of local failure included: presentation with local recurrence, superficial location, and invasion of vital structures (LSS only). Local failure varied significantly with histologic type and was highest in patients with embryonal rhabdomyosarcoma and angiosarcoma. When the data were subjected to multivariate analysis, the following variables emerged as independent predictors of local failure: presentation with local recurrence, surgery by LSS, inadequate margins, angiosarcoma, and invasion of vital structures. These risk factors should be carefully weighed when selecting local treatment for patients with upper extremity soft tissue sarcomas.

Adolescent↗