Biomedical subjects

B Teleky

Publications and source records attributed to B Teleky.

At least 19 recordsLinked to original sources

PubMed2006

Straight and colonic J-pouch reconstruction after low anterior resection.

PURPOSE: A complication after restorative rectal surgery with a straight anastomosis is low-anterior resection syndrome with a postoperatively deteriorated anorectal function. The colonic J-reservoir is sometimes used with the purpose of reducing these symptoms. An alternative method is to use a simple side-to-end anastomosis or a coloplasty. MATERIAL AND METHODS: Three-hundred fiftyseven patients with rectal cancer undergoing total mesorectal excision (TME). Three-hundred (84.0%) received a low anterior resection with primary anastomosis and colo-rectal n = 194 (64.6%) or colo-anal anastomosis n = 106 (35.3%). A colonic pouch using the descending colon was created in 24 patients and in 75 patients respectively. Surgical results and complications were recorded. Patients were followed with a functional evaluation at 6 and 12 months postoperatively. RESULTS: Patient characteristics in both groups were very similar regarding gender, age, tumor level, and Dukes' stages. A large proportion of the patients received short-term preoperative radiotherapy (72%). There was no significant difference in surgical outcome between the 2 techniques with respect to anastomotic height, perioperative blood loss, postoperative complications, reoperations, hospital stay or pelvic sepsis rates except the anastomotic stricture rate in the colonic J-Pouch group after coloanal anastomosis (p < 0.02). CONCLUSIONS: These data show that either a colonic J-pouch or a straight anastomosis performed on the descending colon in low-anterior resection with TME are methods that can be used with similar expected surgical and functional results.

Anal Canal↗

PubMed2005

Preoperative short-term radiation therapy (25 Gy, 2.5 Gy twice daily) for primary resectable rectal cancer (phase II).

To evaluate the feasibility, effectiveness, and long-term bowel function of preoperative hyperfractionated accelerated radiotherapy in primary resectable rectal cancer. A total of 184 consecutive patients (median age 65 years, male : female=2 : 1) with clinical T3Nx rectal adenocarcinoma received preoperative pelvic radiation therapy with single fractions of 2.5 Gy twice daily (interval 6 h between fractions) to a total dose of 25 Gy within 1 week. Surgery was conducted the following week. Postoperative histology revealed UICC stage I in 33%, stage II in 26%, stage III in 34%, and stage IV in 7% of the patients. Median follow-up was 43 months (53 months for surviving patients). The actuarial 4-year-local-recurrence rate was 2.1%, overall recurrence 23%. Disease-specific and disease-free survivals at 4 years (excluding stage IV) were 82 and 69%, respectively. Overall survival for 4 years was 68%. Postoperative mortality was 0.5% (one patient), early anastomotic leakage occurred in 11.4%, and anastomotic stenosis requiring treatment in 6%, of 132 patients with primary anastomosis. Seven of 184 patients (3.8%) died of abdominal complications, all within the first year. Bowel function was satisfactory after more than 5 years. Local control in primarily resectable rectal cancer after 10 x 2.5 Gy is excellent, warranting further evaluation of this treatment.

Adenocarcinoma↗

PubMed2003

The early response of p53-dependent proteins during radiotherapy in human rectal carcinoma and in adjacent normal tissue.

The aim of this study was to investigate the activation of the p53 pathway and the induction of apoptosis during preoperative radiotherapy in normal human rectal tissue and in rectal carcinoma. Twelve patients with rectal cancer of the lower third were enrolled in this study. Tumor specimens and adjacent normal tissue were obtained before radiation, after the third radiation cycle and from the surgically removed rectum. All specimens were analyzed be means of immunohistochemistry for expression of p53 and its downstream target genes MDM2 and p21. In normal mucosal crypts, irradiation led to p53 accumulation and MDM2 induction in more than 70% of the cells. The accumulation of p53 in basal crypts was associated with high expression of p21. Apoptosis was also induced in crypts and occurred in 15% of the cells. Activation of the p53 pathway was not seen in the resting cells at the luminal border of the epithelium. In interstitial cells, p21 was highly upregulated, whereas p53 and MDM2 showed weak expression. The level of bcl-2 was not altered during radiotherapy in healthy tissue. In rectal carcinoma cells, p53 expression was unaltered by irradiation in 11 out of 12 tumors. The p53 non-functional tumors were characterized by a weak induction of MDM2 and p21 and by the lack of apoptosis in the presence of bcl-2. Our findings demonstrate that sequential immunohistochemical analysis is suitable to detect a deregulation of the p53 pathway in human rectal cancer cells during radiotherapy. Further investigations are necessary to elucidate its value as a prognostic marker and potential predictor of therapy responsiveness.

Aged↗

PubMed2001

The differentiation inducers phenylacetate and phenylbutyrate modulate camptothecin sensitivity in colon carcinoma cells in vitro by intracellular acidification.

Aromatic fatty acids such as phenylbutyrate (PB) and its metabolite phenylacetate (PA) induce growth arrest, differentiation and apoptosis in solid tumor cells. Despite their antiproliferative action they were reported to exhibit a synergistic effect in combination with cytotoxic drugs like topotecan, and others. Since the activity of the camptothecines (CPTs) depends on local pH conditions, we investigated, whether PB/PA modulate CPT effects indirectly by affecting intracellular pH in SW620 and SW480 colon cancer cells. The results for the colon carcinoma cells show an antagonistic interaction for the combination of CPT and 0.25-5 mM PA in viability assays, resulting in an approximately 3-fold increase in IC50 (control: 20+/-7 nM). A synergistic effect with significantly increased numbers of late apoptotic/necrotic cancer cells (difference +21+/-4%) and 1.4-fold sensitization were detected upon inclusion of 2.5 mM PA during a 4-h CPT (10 micro;M) loading phase. In response to 0.25-1 mM PA/PB the cells exhibit a reversible decrease of pHi (0.1-0.31 pH units) in HEPES- or bicarbonate-buffered media. Dose-dependent acidification and pHi-recovery occurred following addition of PA and PB after an acid load and inhibition of the Na+/H+-antiporter and bicarbonate exchangers, pointing to a possible intracellular mechanism of cytoplasmic acidification. It is concluded that the synergistic modulation of CPT toxicity by short-term PA/PB treatment in colon carcinoma cells is caused by changes in intracellular pH, possibly affecting quantity and localization of the active closed lactone form of this drug.

Annexin A5↗

PubMed2000

Staining patterns of p53 immunohistochemistry and their biological significance in colorectal cancer.

Immunohistochemistry (IHC) is a cheap and rapid method to detect p53 inactivation but the results are often discordant with gene mutation analysis. This study aimed to investigate whether there is a difference in the immunohistochemical staining patterns of p53-positive cells on comparing tumours with inactivating gene mutations with those without. Tissues of 142 colorectal cancers were investigated for p53 inactivation simultaneously by IHC and gene analysis using SSCP of exons 4-9 and sequencing. In addition, tumours were investigated immunohistochemically for the expression of mdm-2 protein, known to be transcriptionally transactivated by the wild-type (wt) p53 gene. p53-positive cells of tumours without detectable p53 gene mutations were microdissected using a PALM laser microscope system and subjected to p53 sequence analysis. Among the 142 cases of colorectal cancer (male/female=88/54; mean age 66a+/-11 years, range 24-90 years), 74% (n=105) of tumours were positive by p53 IHC and mutations in the p53 gene were found in 51% (73 patients). In 16% (12 patients) with mutations in the p53 gene, IHC for p53 was negative. In tumours with mutations in the p53 gene and positive p53 IHC, staining of all nuclei of the tumour was more frequently (57/61, 93%) found than in tumours without p53 gene mutations, where staining of scattered single cells was predominantly seen (29/44, 66%; p<0.0001). mdm-2 positivity (n=33) showed only staining of scattered single cells, predominantly (24/33, 82%; p<0.0001) in tumours without gene mutations. Single cell microdissection followed by mutation analysis of scattered p53-positive cells revealed no gene mutations. A scattered positive immunohistochemical reactivity of p53 in colorectal cancer cells might therefore represent a functionally active non-mutated p53 gene and should not be considered as a marker of gene mutation and inactivation.

Adenocarcinoma↗

PubMed2000

Detection of focal hepatic lesions: comparison of unenhanced and SHU 555 A-enhanced MR imaging versus biphasic helical CTAP.

The purpose of this study was to compare the diagnostic sensitivity of unenhanced magnetic resonance (MR) imaging, and MR imaging with a new superparamagnetic iron oxide (SPIO)-enhanced contrast agent (SHU 555 A) with biphasic helical computed tomography during arterial portography (CTAP) in patients with focal liver lesions. Eighteen patients with a total of 91 (78 malignant, 13 benign) proven liver lesions underwent unenhanced short tau inversion recovery (STIR), T2-weighted (T2-w) TSE, and SHU 555 A-enhanced T2-w turbo spin-echo (TSE) MR imaging and biphasic helical CTAP. The standard of reference was histopathologic analysis of resected specimens in 59 lesions, intraoperative ultrasound with biopsy in 20 lesions, and CT-guided biopsy and follow-up in 12 lesions. Diagnostic performance of the imaging modalities was compared quantitatively and qualitatively by assessing lesion involvement in liver segments. There were 68 lesions detected on unenhanced T2-w TSE, which resulted in a sensitivity of 75%. With the STIR sequence, 76 lesions were detected, for a sensitivity of 84%, and with SHU 555 A-enhanced MRI, 84 lesions were detected, for a sensitivity of 92%. CTAP detected 88 lesions, for a sensitivity of 97%. The accuracy for unenhanced T2-w TSE was 98%, for STIR 99%, for enhanced-MRI 100%, and for CTAP 95%. The specificity was 100% for SHU 555 A-enhanced MRI and 95% for CTAP. SHU 555 A-enhanced MRI was superior to nonenhanced MRI (P < 0.05) and equivalent to CTAP in terms of sensitivity. Due to the absence of false-positive results on SHU 555 A-enhanced MRI, the specificity and accuracy of enhanced MRI were higher than those of CTAP, but the difference was not statistically significant (P = 0.134).

Adult↗

PubMed2000

p53 gene status and expression of p53, mdm2, and p21Waf1/Cip1 proteins in colorectal cancer.

Abrogation of the normal p53 pathway is the most common molecular alteration in human cancer. p53 Gene status can be potentially assessed through the expression of proteins known to be activated by the wild-type p53 (wt p53) system, such as mdm2 and p21Waf1/Cip1. In this study, the frequency of mdm2, p21Waf1/Cip1, and p53 protein expression was investigated using immunohistochemistry (IHC) in 88 colorectal carcinomas (CRCs). The relationship between these expressions and p53 status was examined. p53 status and the immunophenotypes characterizing these tumors were correlated with standard prognostic variables. Mutation of p53 was detected using single-strand conformational polymorphism (SSCP) analysis and sequencing. Concordance between p53 gene status and p53 immunoreactivity was seen in 62 of 88 (70.45%) carcinomas. Mdm2 expression was found in 22 of 45 (48.88%) and 5 of 43 (11.62%) of the tumors with wt p53 and mutated p53 (P<0.0001), respectively. Predominantly, higher p21Waf1/Cip1 expression was associated with wt p53 (P<0.001). All wt p53 cases that expressed mdm2 also expressed p21Waf1/Cip1. These results suggest that there is a subgroup of CRCs in which p53 is functionally active, inducing transcription of mdm2 and Waf1/Cip1. Their combined evaluation may provide important clues for planning adjuvant systemic therapy and gene therapy based on the restitution of p53 function. However, no significant association was found between the immunophenotypes and the standard prognostic variables investigated.

Adult↗

PubMed2000

Mechanic intestinal obstruction--a possible presentation of perforated appendicitis.

A 61-year-old man presented with diffuse abdominal pain, diarrhea, vomiting and fever. On the initial diagnosis of gastroenteritis the patient received the antibiotic ofloxacine for one week. On admission plain abdominal radiograph suggested a mechanic intestinal obstruction. In computed tomography a conglomerate tumor in the ileocecal region was seen and the patient underwent laparotomy. The conglomerate tumor was mobilized and an abscess opened, which was caused by a perforated appendicitis. After the operation the patient improved immediately and had an uneventful postoperative course. He was released and did not suffer from gastrointestinal symptoms the following 16 months of follow-up. The present case shall set forth that perforated appendicitis can clinically present as intestinal obstruction. Although a rare complication, perforated appendicitis should therefore even be considered in cases of mechanic intestinal obstruction of unknown cause.

Abscess↗

PubMed2000

Phase II study of gemcitabine in combination with cisplatin in patients with locally advanced and/or metastatic pancreatic cancer.

The present phase II trial was performed to assess the efficacy and toxicity of polychemotherapy with gemcitabine and cisplatin in patients with locally advanced or metastatic carcinoma of the pancreas. Sixteen patients received six courses of an i.v. cytotoxic regimen consisting of gemcitabine (1000 mg/m2, days 1, 8 and 15) and cisplatin (35 mg/m2, days 1, 8 and 15) administered in 28-day intervals. Complete remission (CR) occurred in one patient (6%), partial remission (PR) in four patients (25%) and stable disease in seven patients (44%), whereas four patients (25%) developed progressive disease resulting in an overall response rate of 31%. Mean duration of responses (CR+PR) was 3.6 (range 0.7-8.5) months and mean time to progression was 7.4 (range 3.8-12.6) months. After a mean observation period of 11.5 months the overall survival was 9.6 months with 12 patients (75%) still being alive, which compares favorably with historical data of the administration of gemcitabine alone. The performance status improved in three (19%) and stabilized in eight (50%) out of 16 patients for 4 weeks or longer. Treatment-associated toxicity included alopecia of WHO grade III in all cases, leukopenia of WHO grades I and II in 10 patients (63%), grade III in five patients (31%), and thrombocytopenia grades I and II in four patients (25%), and grades III and IV in 10 patients (63%). We conclude that the administered dosage and schedule of gemcitabine and cisplatin in patients with locally advanced or metastatic cancer of the pancreas constitutes an active cytotoxic regimen associated with moderate toxicity.

Adenocarcinoma↗

PubMed1999

Abdominosacral resection of recurrent rectal cancer in the sacrum.

PURPOSE: Resection of the sacrum is the only curative therapy of isolated sacral recurrence after primarily resected rectal cancer. The aim of the study was to assess whether there is a benefit in terms of overall survival, morbidity, and mortality when sacrum resection is performed more radically and in cooperation between colorectal and orthopedic surgeons. Possible prognostic factors were also assessed. METHODS: Twelve consecutive patients who underwent interdisciplinary partial sacral resection were included in a retrospective cohort study. Furthermore, overall survival rate and survival time were calculated. RESULTS: Histologic examination showed tumor-free resection margins in all cases. Extended resection was necessary in seven patients, including total pelvic exenteration in two. No perioperative death occurred and no patient required early reoperation. Complications were observed in 42 percent of patients, mainly caused by poor wound healing. All patients experienced relief from pain. One-year and three-year overall survival rates were 50 and 17 percent, respectively. The overall mean survival time was 21.7 months. Patients who died of recurrent disease within one year either underwent former resection for locoregional recurrence, had extensive local recurrent tumors affecting pelvic visceral structures, or retrospectively suffered from metastatic sacral tumor manifestation. CONCLUSION: The mortality and morbidity rates observed in the present study seem to justify partial sacral resection as a means to achieve palliation of perineosacral pain in spite of rare overall long-term survival.

Adenocarcinoma↗

PubMed1999

Bacteroides fragilis toxin 2 damages human colonic mucosa in vitro.

BACKGROUND: Strains of Bacteroides fragilis producing a 20 kDa protein toxin (B fragilis toxin (BFT) or fragilysin) are associated with diarrhoea in animals and humans. Although in vitro results indicate that BFT damages intestinal epithelial cells in culture, the effects of BFT on native human colon are not known. AIMS: To examine the electrophysiological and morphological effects of purified BFT-2 on human colonic mucosa in vitro. METHODS: For resistance (R) measurements, colonic mucosa mounted in Ussing chambers was exposed to luminal or serosal BFT-2 (1.25-10 nM) and after four hours morphological damage was measured on haematoxylin and eosin stained sections using morphometry. F actin distribution was assessed using confocal microscopy. RESULTS: Serosal BFT-2 for four hours was four-, two-, seven-, and threefold more potent than luminal BFT-2 in decreasing resistance, increasing epithelial 3H-mannitol permeability, and damaging crypt and surface colonocytes, respectively (p<0.05). Confocal microscopy showed reduced colonocyte F actin staining intensity after exposure to BFT-2. CONCLUSIONS: BFT-2 increases human colonic permeability and damages human colonic epithelial cells in vitro. These effects may be important in the development of diarrhoea and intestinal inflammation caused by B fragilis in vivo.

Actins↗

PubMed1999

Effects of substance P on human colonic mucosa in vitro.

Previous studies indicated that the peptide substance P (SP) causes Cl--dependent secretion in animal colonic mucosa. We investigated the effects of SP in human colonic mucosa mounted in Ussing chamber. Drugs for pharmacological characterization of SP-induced responses were applied 30 min before SP. Serosal, but not luminal, administration of SP (10(-8) to 10(-6) M) induced a rapid, monophasic concentration and Cl--dependent, bumetanide-sensitive short-circuit current (Isc) increase, which was inhibited by the SP neurokinin 1 (NK1)-receptor antagonist CP-96345, the neuronal blocker TTX, the mast cell stabilizer lodoxamide, the histamine 1-receptor antagonist pyrilamine, and the PG synthesis inhibitor indomethacin. SP caused TTX- and lodoxamide-sensitive histamine release from colonic mucosa. Two-photon microscopy revealed NK1 (SP)-receptor immunoreactivity on nerve cells. The tyrosine kinase inhibitor genistein concentration dependently blocked SP-induced Isc increase without impairing forskolin- and carbachol-mediated Isc increase. We conclude that SP stimulates Cl--dependent secretion in human colon by a pathway(s) involving mucosal nerves, mast cells, and the mast cell product histamine. Our results also indicate that tyrosine kinases may be involved in this SP-induced response.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

Outcomes of surgical, percutaneous endoscopic, and percutaneous radiologic gastrostomies.

OBJECTIVES: To evaluate and compare outcomes and complications in patients having undergone gastrostomy by surgical (SG), percutaneous endoscopic (PEG), or percutaneous radiological (PRG) procedure. DESIGN: Retrospective analysis. SETTING: University-based tertiary care center. PATIENTS: Of 82 patients who met inclusion criteria, 14 patients (median age, 40 years) received a surgical tube placement (SG), in 24 patients (median age, 55 years) a PEG procedure was performed, and in 44 patients (median age, 57 years) the tube was placed under fluoroscopic guidance (PRG). Indications for gastrostomy were similar in all groups, representing mainly cancer of the oropharyngeal, head and neck region (51 [61%]) as well as the upper gastrointestinal tract (6 [8%]), neurological disorders (15 [18%]), and others (10 [13%]). MAIN OUTCOME MEASURES: Catheter function rates, major and minor procedure-related complications, and survival. RESULTS: Median follow-up was 17.2 months. Ten patients (71%) died in the SG group 7 to 855 days (median, 67 days) after the procedure, 7 patients (29%) died 5 to 263 days (median, 103 days) after PEG placement, and 30 patients (68%) died within 3 to 621 days (median, 112 days) after PRG, of their underlying disease or disease-related complications; 1 procedure-related death occurred 6 days after radiological tube placement. We observed a rate of minor complications of 43% (6 patients), 33% (8), and 36% (16) and a major complication rate of 14% (2 patients), 17% (4), and 11% (5) in the SG, PEG, and PRG groups, respectively. Tube function rates at 1 year were 67% (9 patients) and 68% (20) in the SG and PEG groups, respectively, and 10% lower (39) in the PRG group, although the difference was not statistically significant. CONCLUSIONS: There is no major difference between SG, PEG, and PRG concerning procedure-related complications. Tube function tends to be inferior after radiological tube placement.

Adolescent↗

PubMed1998

Stage-dependent therapy of rectal carcinoid tumors.

Although malignant behavior of rectal carcinoid tumors is rare, the risk of metastases and death does exist. Adaptation of therapy according to the estimated malignancy seems necessary. To develop a stage-dependent therapy, 31 patients with rectal carcinoid tumors measuring 5 to 50 mm in diameter were analyzed retrospectively. Malignancy was estimated according to tumor size, infiltration depth, and histopathology. There were 18 tumors within the mucosa and submucosa (T1), 7 tumors with muscularis propria invasion (T2), and carcinoid tumor penetrating the full rectal wall (T3) or spreading to surrounding tissue (T4) in 6 patients. Altogether 20 patients (65%) were treated with a minimally invasive intervention: endoscopic polypectomy (EP) in 12 and transanal excision (TE) in 8 patients. In 11 patients (35%) aggressive surgical procedures--anterior resection (AR) in 4 and abdominoperineal resection (APR) in 7--were performed. After a mean +/- SD follow-up of 86.0 +/- 61.3 months, tumor recurrence was not seen in any of the 20 patients with minimally invasive treatment, and all were still alive. No severe complications associated with surgical procedures were detected. In contrast, 5 of the 10 patients with advanced tumor stage died from their disease despite aggressive surgery (AR, APR). In conclusion, depending on tumor stage, treatment of rectal carcinoids includes EP, TE, or extended resection. Minimally invasive techniques are safe treatments for small to medium-size T1/T2 rectal carcinoids. Extended surgery cannot improve the overall survival of those with advanced tumors (T3/T4, N1, M1) but can be beneficial for preventing local complications.

Adult↗

PubMed1998

It is possible to omit postoperative irradiation in a highly selected group of elderly breast cancer patients.

The purpose of this study was the evaluation of the necessity of routinely applied postoperative radiotherapy in a highly selected patient-group after breast conserving surgery. Between 1983 and May 1994, 356 women over 60 years of age with Stage I or II breast cancer were treated by quadrantectomy and axillary dissection followed by either adjuvant irradiation or no radiotherapy. We have analysed our data retrospectively to investigate whether irradiation has any benefit in elderly patients with respect to locoregional recurrence rates. After a median follow-up of 60 months the multivariate model revealed lymph node status (p = 0.002) as highly significant with regard to local recurrence free survival. We were not able to identify a positive effect of adjuvant irradiation in patients with negative lymph nodes and positive receptor status: both patient groups with or without irradiation had similar locoregional recurrence rates of 3%. In a subgroup of patients who were lymph node negative, receptor positive, and received adjuvant tamoxifen therapy, the local recurrence rates were as low as 2% in both groups. Concerning these results it may be possible to avoid the morbidity and potential psychological side effects of radiotherapy in breast cancer patients over 60 years of age treated by breast conserving surgery (T1, N0, positive hormone receptor, adjuvant tamoxifen) without increasing risk of locoregional recurrence. These data have to be confirmed in a prospectively randomized fashion.

Aged↗

PubMed1998

Visualization of intestinal splenosis by somatostatin receptor scintigraphy.

A case of intestinal splenosis in a splenectomized patient is presented. (111)In-DTPA-D-Phe-1-octreotide ((111)In-OCT) scintigraphy, computed tomography, as well as magnetic resonance imaging suggested a tumor in the small intestine. The histopathological finding after operation revealed an intestinal splenosis. This case illustrates that intestinal splenosis may mimic a tumor by (111)In-OCT scan. In a splenectomized patient, a splenosis should therefore be considered.

Adult↗

PubMed1998

Abdomiosacral resection of recurrent rectal cancer in the sacrum.

Isolated manifestation of recurrent rectal cancer in the pelvis after primary radical resection occurs in 7 to 33% and frequently causes severe sacral pain. Sacral recurrence gravely impairs the quality of life as well as life expectancy. Irradiation offers a means of palliation. However, even if radiation is effectful it only provides symptomatic recurrent tumors frequently remain radioresistant 1.4. Only portal sacral resection potentially provides curative treatment if the Recurrent tumor is limited to the sacrum. Without surgical therapy the life expectancy of patients with local recurrence of rectal cancer is about 7 months.

Abdomen↗

PubMed1998

[Results of interdisciplinary sacrum resection in sacral recurrence of rectal carcinoma].

The authors present a retrospective analysis of 12 consecutive patients surgically treated with curative intention for recurrent rectal cancer involving the sacrum. After radical partial sacral resection--extended resection in seven cases--the operative mortality rate was zero, postoperative long-term survival was reached in 17%, while effective palliation of pain was achieved in all cases. Nevertheless, 50% did not survive more than 1 year after the operation. The overall mean survival time was 22 months. Sacral recurrence can be resected safely and potentially curatively after careful patient selection.

Combined Modality Therapy↗