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Biomedical subjects

F Meric

Publications and source records attributed to F Meric.

At least 19 recordsLinked to original sources

Breast conservation therapy as a treatment option for the elderly. The M. D. Anderson experience.

BACKGROUND: Although almost half of all incidents of breast carcinoma occur in women age > or = 65 years, not enough is known about appropriate care for patients in this age group. The objective of the current study was to evaluate the role of breast conservation therapy in the management of breast carcinoma in women age > or = 65 years. METHODS: From 1970 to 1994, 1325 patients with carcinoma of the breast were treated with breast conservation therapy (segmental mastectomy and radiation therapy with or without axillary lymph node dissection) at The University of Texas M. D. Anderson Cancer Center. From this patient group, the authors identified 184 elderly women (> or = 65 years) with Stage 0-III disease at the time of diagnosis. RESULTS: The median patient age was 70 years (range, 65-88 years). The distribution of disease by stage among the women was Stage 0 disease in 12 patients (7%), Stage I disease in 107 patients (58%), Stage II disease in 63 patients (34%), and Stage III disease in 2 patients (1%). Comorbid conditions that may have influenced treatment planning were reported in 91 patients (50%). An axillary lymph node dissection was performed in 135 patients (73%), with positive axillary lymph nodes found in 30 patients (22%). Adjuvant chemotherapy was given to 10 patients (5%), and tamoxifen therapy was given to 63 patients (34%). Complications from treatment were reported in 24 patients (13%). With a median follow-up of 7.3 years (range, 0.25-23.5 years), 9 patients developed locoregional disease recurrence (5%), 10 patients developed contralateral breast carcinoma (5%), and 21 patients developed distant metastasis (11%). At last follow-up, 113 patients (61%) were alive, 15 patients (8%) were dead of disease, and 56 patients (30%) were dead of other causes. The 5-year and 10-year disease specific survival rates were 96% and 91%, respectively. CONCLUSIONS: Breast conservation therapy with segmental mastectomy and postoperative radiation therapy with or without axillary lymph node dissection provides excellent local control and disease free survival in elderly women with breast carcinoma. This treatment should be considered as the standard of care for elderly patients without severe comorbid disease.

Aged↗

Utility of breast sentinel lymph node biopsy using day-before-surgery injection of high-dose 99mTc-labeled sulfur colloid.

BACKGROUND: In sentinel lymph node (SLN) biopsy for breast cancer, many centers use same-day preoperative injection of technetium 99mTc-labeled sulfur colloid and intraoperative injection of blue dye for localization of SLNs. Same-day sulfur colloid injections can be problematic because of the variability in sulfur colloid migration times, which can lead to ineffective use of operating room time, and low SLN-to-background radioactivity ratios. We examined the utility of day-before-surgery injections of high dose 99mTc-labeled sulfur colloid injections. METHODS: The day before surgery, high-dose 99mTc-labeled sulfur colloid was injected peritumorally, and a lymphoscintigram was obtained. Intraoperatively, after injection of blue dye, a gamma probe was used to localize SLNs. Nodes that were stained blue or were highly radioactive were considered SLNs and were removed. RESULTS: Lymphoscintigraphy demonstrated drainage in 107 patients (91%). Transcutaneous localization of the SLN was possible in 104 patients (89%). In three patients, all of whom had no drainage demonstrated on lymphoscintigraphy, no SLN was identified at surgery (97.5% success rate for SLN identification). A mean of 2.3 SLNs per patient were identified. Twenty-five patients (21%) had at least one histologically positive SLN. In 23 of these patients, the positive SLN was the SLN with the most radioactivity, and in the remaining two patients, the positive SLN was both blue-stained and hot. CONCLUSION: Day-before-surgery injection of high-dose 99mTc-labeled sulfur colloid results in high rates of transcutaneous and intraoperative identification of SLNs. The delay between injection and surgery did not appear to promote significant passage of sulfur colloid to second-echelon nodes.

Adult↗

Impact of neoadjuvant chemotherapy on postoperative morbidity in soft tissue sarcomas.

PURPOSE: The purpose of this study was to test the hypothesis that neoadjuvant chemotherapy (NeoCT) does not increase morbidity in patients undergoing radical surgery for soft tissue sarcomas. PATIENTS AND METHODS: The records of 309 patients who presented to The University of Texas M.D. Anderson Cancer Center for definitive surgical management of primary soft tissue sarcomas were retrospectively reviewed. One hundred five patients who received NeoCT were compared with 204 patients who had surgery first (Surg). Patients had extremity sarcomas (71 NeoCT patients and 130 Surg patients) or retroperitoneal/visceral sarcomas (34 NeoCT and 74 Surg). RESULTS: NeoCT patients had larger tumors (median, 12 v 8 cm), more frequently had high-grade tumors (90% v 64%), and were younger (median age 47 v 55 years). The incidence of surgical complications was not different for NeoCT patients than for Surg patients, both in those with extremity sarcomas (34% v 41%) and in those with retroperitoneal/visceral sarcomas (29% v 34%). The most common complications were wound infections and other wound complications. Preoperative radiation therapy, autologous flap coverage, and extremity tumors were associated with increased wound complications. No significant differences in length of hospital stay, rate of readmission, or rate of reoperation for complications were found between the NeoCT and Surg groups. One of the three postoperative deaths in our series occurred in the NeoCT group. CONCLUSION: In this retrospective review, there was no evidence that NeoCT increased postoperative morbidity in patients with soft tissue sarcomas. Prospective, randomized studies are needed to confirm these results.

Antibiotics, Antineoplastic↗

Prognostic implications of pathological lymph node status after preoperative chemotherapy for operable T3N0M0 breast cancer.

BACKGROUND: Although preoperative chemotherapy has become the standard of care for inoperable locally advanced breast cancer, its role for downstaging resectable primary tumors is still evolving. The purpose of this study was to determine whether the prognostic information from an axillary node dissection in patients with clinical T3N0 breast cancer was altered by preoperative chemotherapy compared with surgery de novo. METHODS: Between 1976 and 1994, 91 patients with clinically node-negative operable T3 breast cancer received doxorubicin-based combination chemotherapy on protocol at one institution. Fifty-three patients received both preoperative and postoperative chemotherapy (PreopCT), and 38 received postoperative chemotherapy only (PostopCT). All patients underwent axillary lymph node dissection as part of their definitive surgical treatment. There were no differences between the PreopCT and PostopCT groups in median age (51 vs. 49 years), median tumor size at presentation (6 cm vs. 6 cm), tumor grade, or estrogen receptor status (estrogen receptor negative 38% vs. 32%). The median follow-up time was 7 years. RESULTS: Patients in the PreopCT group had fewer histologically positive lymph nodes (median, 0 vs. 3, P < .01), and a lower incidence of extranodal extension (19% vs. 42%, P = .02). By univariate analysis, the number of pathologically positive lymph nodes (P < .01) and extranodal extension (P < .01) were predictors of disease-specific survival in PreopCT patients. Multivariate analysis showed that extranodal extension was the only independent prognostic factor in PreopCT patients (P < .01). Overall, PreopCT and PostopCT patients had similar 5-year disease-free survival rates (66% vs. 57%); however, PreopCT patients had worse disease-free (P = .01) and disease-specific survival (P = .04) when survival was compared after adjustment for the number of positive lymph nodes. Furthermore, PreopCT patients with 4-9 positive lymph nodes had a lower 5-year disease-free survival rate than PostopCT patients with 4-9 positive nodes (17 vs. 48%, P = .04). CONCLUSIONS: Axillary lymph node status remains prognostic after chemotherapy. Pathologically positive lymph nodes after preoperative chemotherapy are associated with a worse prognosis than the same nodal status before chemotherapy.

Adult↗

Surgery after downstaging of unresectable hepatic tumors with intra-arterial chemotherapy.

BACKGROUND: This retrospective study was performed to assess the outcome among patients who underwent hepatic resection or tumor ablation after hepatic artery infusion (HAI) therapy down-staged previously unresectable hepatocellular carcinoma (HCC) or liver metastases from colorectal cancer (CRC). METHODS: Between 1983 and 1998, 25 patients with HCC and 383 patients with hepatic CRC metastases were treated with HAI therapy for unresectable liver disease. We retrospectively reviewed the records of 26 (6%) of these patients who underwent subsequent surgical exploration for tumor resection or ablation. RESULTS: At a median of 9 months (range 7-12 months) after HAI treatment, four patients (16%) with HCC underwent exploratory surgery; two underwent resection with negative margins, and the other two were given radiofrequency ablation (RFA) because of underlying cirrhosis. At a median postoperative follow-up of 16 months (range 6-48 months), all four patients were alive with no evidence of disease. At a median of 14.5 months (range 8-24 months) after HAI therapy, 22 patients with hepatic CRC metastases underwent exploratory surgery; 10 underwent resection, 6 underwent resection and RFA or cryotherapy, and 2 underwent RFA only. At a median follow-up of 17 months, 15 (83%) of the 18 patients with CRC who had received surgical treatment had developed recurrent disease; the other 3 died of other causes (1 of postoperative complications) within 7 months of the surgery. One patient in whom disease recurred underwent a second resection and was disease-free at 1 year follow-up. CONCLUSIONS: Hepatic resection or ablation after tumor downstaging with HAI therapy is a viable option for patients with unresectable HCC. However, given the high rate of recurrence of metastases from CRC, hepatic resection or ablation after downstaging with HAI should be used with caution.

Adult↗

Ductal carcinoma-in-situ: long-term results of breast-conserving therapy.

BACKGROUND: The role of breast-conserving therapy (BCT) in the management of ductal carcinoma-in-situ (DCIS) is controversial because of reported high recurrence rates. We reviewed our experience to determine whether the rate and pattern of locoregional recurrence after BCT were similar in patients with DCIS and patients with early-stage (T1) invasive breast tumors and whether local recurrence affected survival. METHODS: Between 1973 and 1994, 87 patients with DCIS alone, 22 patients with DCIS with microinvasion (DCIS-M), and 646 patients with invasive breast cancer 2 cm or smaller in diameter were treated with BCT (wide local excision with radiotherapy) at The University of Texas M. D. Anderson Cancer Center. Survival was calculated by the Kaplan-Meier method. The median follow-up times were 11 years for patients with DCIS alone, 12 years for patients with DCIS-M, and 8 years for patients with invasive breast cancer. RESULTS: Eleven (13%) of 87 patients with DCIS and 5 (23%) of 22 patients with DCIS-M had developed locoregional recurrences at follow-up. Two patients with DCIS with locoregional recurrence died of breast cancer. Of the 646 patients with invasive breast cancer, 56 (9%) had a locoregional recurrence, and 16 (2%) died of breast cancer. The median time to locoregional recurrence was significantly longer in patients with DCIS or DCIS-M (9-10 years) than patients with invasive tumors (5 years). CONCLUSIONS: DCIS is a favorable disease with an excellent long-term survival. The locoregional recurrence rate in patients with DCIS treated with BCT is similar to that in patients with early-stage invasive breast cancer treated with BCT, but time to locoregional recurrence is significantly longer in patients with DCIS. In patients with DCIS treated with BCT, intense surveillance for locoregional recurrence needs to be maintained for the patient's lifetime.

Adult↗

A treatment algorithm for pneumothoraces complicating central venous catheter insertion.

BACKGROUND: We investigated the role of observation or insertion of a small French pigtail catheter with Heimlich valve as alternative management to a tube thoracostomy for iatrogenic pneumothorax complicating central venous catheter (CVC) insertion. METHODS: A retrospective review of 9,637 consecutive patients who had had subclavian CVCs inserted on an outpatient basis identified 100 patients with pneumothoraces. Treatment consisted of (1) observation, (2) outpatient insertion of a Heimlich valve, or (3) inpatient tube thoracostomy. RESULTS: The median pneumothorax size was 10% (range 1% to 100%). Fifty-eight patients had observation as initial treatment, and this strategy was successful in 35 (60%). Thirty-four patients were treated initially with Heimlich valves, and this strategy was successful in 29 (85%). Tube thoracostomy as initial therapy was successful in 7 (88%) of 8 patients. Patients in who initial treatment failed were treated with insertion of a Heimlich valve or tube thoracostomy. CONCLUSION: In appropriately selected patients, pneumothorax after insertion of a subclavian CVC can be successfully managed in the outpatient setting with observation. Patients in whom observation fails can be treated with insertion of a Heimlich valve. Tube thoracostomy can be reserved for refractory PTX or emergent situations.

Ambulatory Care↗

Laparoscopic excision of a rare type II choledochal cyst: case report and review of the literature.

Although once considered rare, choledochal cysts now are extensively reported on and have an official anatomic classification. The authors report a case of a 4-year-old girl whom on routine abdominal ultrasound as follow-up for vesicoureteral reflux was found to have a choledochal cyst. Follow-up hepatobiliary scan together with the ultrasound findings was consistent with a rare type II choledochal cyst. On laparoscopy, a type II choledochal cyst was confirmed on dissection and amenable to laparoscopic excision. Intraoperative cholangiogram after excision showed normal remaining biliary anatomy. The patient was discharged the following day without delayed complications on follow-up visits. This report suggests a role for laparoscopic surgery in the definitive management of selected cases of choledochal cystic disease. (Included is relevant radiological documentation, illustration of technique, and review of the literature.)

Child, Preschool↗

Congenital cholesteatoma of the mastoid region.

Congenital cholesteatoma may arise in the petrous apex, mastoid, middle ear, or external auditory canal. The least common site being the mastoid process. We present one case of primary mastoid cholesteatoma confirmed by clinical examination, surgical findings and radiological evaluation.

Aged↗

Chondrosarcoma of the nasal septum.

Chondrosarcoma of the nasal septum is a rather uncommon tumour. Therefore, only limited numbers of cases have been described in the literature. This paper reveals one more case observed at the ORL department of Dicle University. In the present case, by using a transnasal and transpalatal approach, total resection of the tumour was performed in conjunction with postoperative radiotherapy.

Adult↗

Adenovirus 5 early region 1A does not induce expression of the ewing sarcoma fusion product EWS-FLI1 in breast and ovarian cancer cell lines.

The adenovirus 5 early region 1A (E1A) can function as a tumor suppressor gene and is being used in clinical trials as a therapeutic agent for advanced breast, ovarian, and head and neck cancer. Recently, there has been a dispute regarding whether transfection with the E1A gene can induce expression of the Ewing sarcoma oncogenic fusion transcript EWS-FLI1 (Sanchez-Prieto et al., Nat. Med., 5: 1076-1079, 1999; Melot and Delattre, Nat. Med., 5: 1331, 1999; Kovar et al., Cancer Res., 60: 1557-1560, 2000). In an effort to settle the controversy, we tested several stable E1A transfectants of cell lines MDA-MB-231, MCF-7, MDA-MB-435 (breast cancer), SKOV3-ipl (ovarian cancer), and PC-3 (prostate cancer), as well as parental and vector-transfected controls, HEK 293 cells, and RD-ES (Ewing sarcoma) cells, for the EWS-FLI1 fusion product. The EWS-FLI1 transcript could not be identified with reverse transcription-PCR in any of the 13 E1A-transfected cell lines analyzed. Furthermore, the EWS-FLI1 fusion protein could not be detected by Western blot analysis in E1A-transfected cell lines. These results suggest that E1A transfection does not necessarily lead to expression of the oncogenic EWS-FLI1 fusion transcript. Thus, the potential induction of this gene rearrangement by E1A gene therapy is unlikely to be clinically significant in the treatment of advanced malignant disease.

Adenovirus E1A Proteins↗

Transcriptional repression by XPc1, a new Polycomb homolog in Xenopus laevis embryos, is independent of histone deacetylase.

The Polycomb group (Pc-G) genes encode proteins that assemble into complexes implicated in the epigenetic maintenance of heritable patterns of expression of developmental genes, a function largely conserved from Drosophila to mammals and plants. The Pc-G is thought to act at the chromatin level to silence expression of target genes; however, little is known about the molecular basis of this repression. In keeping with the evidence that Pc-G homologs in higher vertebrates exist in related pairs, we report here the isolation of XPc1, a second Polycomb homolog in Xenopus laevis. We show that XPc1 message is maternally deposited in a translationally masked form in Xenopus oocytes, with XPc1 protein first appearing in embryonic nuclei shortly after the blastula stage. XPc1 acts as a transcriptional repressor in vivo when tethered to a promoter in Xenopus embryos. We find that XPc1-mediated repression can be only partially alleviated by an increase in transcription factor dosage and that inhibition of deacetylase activity by trichostatin A treatment has no effect on XPc1 repression, suggesting that histone deacetylation does not form the basis for Pc-G-mediated repression in our assay.

Amino Acid Sequence↗

Latex sensitization in general pediatric surgical patients: a call for increased screening of patients.

BACKGROUND/PURPOSE: Latex sensitization is a well-documented occurrence in children with myelodysplastic and urologic anomalies. The incidence of latex allergy in general pediatric surgical patients, however, has not been previously addressed. The purpose of this study was to examine the risk of perioperative latex reactions in a general pediatric surgical practice over a 1-year period. METHODS: This study examined the occurrence of latex sensitization using two methods. First, the preoperative anesthesia records of patients that have undergone surgery from October 1995 through September 1996 at Mott Children's Hospital were reviewed retrospectively. Second, all patients who had intraoperative anaphylaxis attributable to latex sensitization, including those from three additional hospitals, were evaluated. RESULTS: During a 12-month period, 1,523 pediatric general surgical operations were performed at the C.S. Mott Children's Hospital. Of these, only 11 operations on five patients were performed under latex precautions. All of these patients had a preoperative diagnosis of latex sensitivity. During the same period, intraoperative anaphylactic reactions caused by latex allergy occurred in two of the general surgical patients (0.13%) at the C.S. Mott Hospital. Four additional cases are also reported from other study hospitals. None of these patients were suspected, based on current screening methods, of having a latex allergy before their surgery. CONCLUSIONS: Latex allergy is a potentially life-threatening condition in the pediatric general surgical population. Further study is needed to develop criteria to preoperatively identify patients at risk for latex sensitization.

Adolescent↗

Regulated unmasking of in vivo synthesized maternal mRNA at oocyte maturation. A role for the chaperone nucleoplasmin.

We examine the translational regulation of histone H4 mRNA when Xenopus laevis oocytes are induced to mature with progesterone. Histone H4 mRNA synthesized from plasmid templates microinjected into oocyte nuclei is translationally silenced (masked). This masked mRNA becomes translationally active only after oocyte maturation. In contrast, histone H4 mRNA injected into the oocyte cytoplasm is translationally active both before and after oocyte maturation. Thus, transcription in vivo is required to mask histone H4 mRNA and to allow subsequent translational regulation. Protein association with histone H4 mRNA synthesized in vivo was determined before and after oocyte maturation. UV cross-linking of radiolabeled RNA to protein and immunoprecipitation of cross-linked proteins reveals an increased association of the chaperone nucleoplasmin with ribonucleoprotein particles dependent on the oocyte maturation process. The Y-box protein FRGY2 inhibits translation of histone H4 mRNA in vitro. Nucleoplasmin is able to partially relieve this repression. We discuss the potential role of nuleoplasmin in the remodeling of repressive ribonucleoprotein particles containing maternal mRNA to facilitate translational activation.

Amino Acid Sequence↗

Masking and unmasking maternal mRNA. The role of polyadenylation, transcription, splicing, and nuclear history.

We establish that masked mRNAs synthesized from exogenous plasmid templates microinjected into the nuclei of Xenopus oocytes are translationally activated (unmasked) on oocyte maturation concomitant with polyadenylation. Synthetic mRNA injected into the cytoplasm of the oocyte is translated over an order of magnitude more efficiently than is the cognate mRNA synthesized in vivo. Both mRNA synthesized in vivo and mRNA microinjected into the oocyte cytoplasm require a cytoplasmic polyadenylation element in the 3'-untranslated region to activate translation on maturation. Although polyadenylation upon oocyte maturation can relieve the translational repression of mRNA synthesized in vivo, the excision of an intron within the nucleus does not relieve repression. We suggest that the translational repression coupled to the transcription process will more effectively repress inappropriate gene expression in the oocyte and offer the potential to achieve a wider range of gene regulation.

Animals↗

Translational repression dependent on the interaction of the Xenopus Y-box protein FRGY2 with mRNA. Role of the cold shock domain, tail domain, and selective RNA sequence recognition.

We have examined the determinants of the translational repression of mRNA by the Xenopus oocyte-specific Y-box protein FRGY2 using in vitro and in vivo assays. In vitro reconstitution of messenger ribonucleoprotein (mRNP) complexes demonstrates that the sequence-specific RNA-binding cold shock domain is not required for translational repression, whereas the RNA-binding C-terminal tail domain is essential. However, microinjection of reconstituted mRNPs into Xenopus oocytes demonstrates that although translational repression occurs in the absence of consensus RNA binding sequences for FRGY2, the presence of FRGY2 recognition elements within mRNA potentiates translational repression. Analysis of the in vivo assembly of mRNP shows that the cold shock domain alone is not stably incorporated into mRNP, whereas the C-terminal tail domain is sufficient for stable incorporation. We suggest that translational repression of mRNA by FRGY2 is favored by sequence-selective recognition of RNA sequences by the cold shock domain. However, translational repression in vitro and the assembly of mRNP in vivo requires the relatively nonspecific interaction of the C-terminal tail domain with mRNA. Thus two distinct domains of FRGY2 are likely to contribute to translational control.

Animals↗

Coupling transcription to translation: a novel site for the regulation of eukaryotic gene expression.

Recent experiments using Xenopus oocytes demonstrate that the history of a particular mRNA in the nucleus can influence the efficiency with which that mRNA will be utilized by the translational machinery. Individual promoter elements, specific protein-RNA interactions and the splicing process within the nucleus can all influence translational fate within the cytoplasm. Central to the regulatory mechanisms influencing the translation process is the packaging of mRNA by a highly conserved family of Y-box proteins. These Y-box proteins are found in cytoplasmic messenger ribonucleoprotein particles where they have a causal role in restricting the recruitment of mRNA to the translational machinery. Nuclear processes influence the packaging of mRNA by the Y-box proteins in the cytoplasm and in consequence mRNA translation. This functional coupling provides a novel site for the regulation of eukaryotic gene expression.

Animals↗

Prevention of radiation enteritis in children, using a pelvic mesh sling.

Between 1986 and 1991, the authors used polyglycolic acid mesh slings (placed at or above the sacral promontory) in eight children with pelvic malignancies to exclude all small bowel from the pelvis during pelvic radiation therapy. The only complications of this treatment were prolonged postoperative ileus (one patient) and temporary, partial small bowel obstruction (one patient). The average amount of radiation administered to the pelvis postoperatively was 5,349 +/- 556 cGy. In one of the eight patients, gastrointestinal symptoms (diarrhea for 24 hours) developed during radiation therapy. Early radiological evaluation confirmed that the small bowel was out of the pelvis in all five of the patients studied. Mesh disruption occurred between 2 and 5 months postoperatively (mean, 3.4 +/- 1.5 months) and was often identified symptomatically by the patient. Seven of the eight survived, with disease remission in six. Pelvic disease was absent at the time of death in the one patient who did not survive. Throughout the follow-up period (mean, 20 months) no survivor has had delayed symptoms of radiation enteritis. In children with pelvic malignancies in whom aggressive application of pelvic irradiation is required, the use of an absorbable pelvic mesh sling appears efficacious in preventing radiation-associated enteritis.

Child↗