Biomedical subjects

R Jakesz

Publications and source records attributed to R Jakesz.

At least 37 records · Page 2Linked to original sources

PubMed2001

[Surgery for non-colorectal and non-neuroendocrine liver metastases].

INTRODUCTION: Hepatic resection has been shown to prolong survival in selected patients with colorectal liver metastases. Due to slow tumor growth patients with neuroendocrine liver metastases tend to have a good prognosis and benefit from chemo-embolisation and symptomatic treatment. The role of surgery in treating non-neuroendocrine and non-colorectal liver metastases is discussed controversially, due to the limited knowledge on this subject. The aim of our study was, therefore, to evaluate our own experiences with hepatic surgery for non-neuroendocrine, non-colorectal liver metastases. METHODS: A retrospective review of 72 patients (median age 60.9 years) who underwent 73 hepatic resections for non-neuroendocrine, non-colorectal liver metastases between 1980 and 2000 at a single tertial referral center was carried out. RESULTS: Hepatic resection was combined with surgery for the primary tumor in 30 cases (41.1%). Hospital mortality was 4.2%. 35 patients (47.9%) developed complications. The mean hospital stay was 17.5 days. In 64.4% of the cases a potentially curative resection was reached. Overall actuarial survival was 52.1% at 1 year, 25.3% at 3 years and 9.9% at 5 years. The respective median overall survival times were 7.1 months (gastric cancer metastases; n = 15), 4.9 months (cholangiocellular cancer metastases; n = 9), 5.6 months (gall bladder, bile duct cancer metastases; n = 8), 35.4 months (kidney cancer metastases; n = 8), 14.4 months (breast cancer metastases; n = 4), 15.3 months (pancreas and other adenocarcinoma metastases; n = 11), 49.9 months (sarcoma metastases; n = 10) and 32.9 months (other metastases; n = 7). CONCLUSIONS: In isolated hepatic metastases originating from sarcoma and hypernephroma radical resection can prolong survival. However, surgery cannot improve the prognosis in patients with liver metastases originating from the pancreas, gallbladder and the biliary tract. In selected patients with liver metastases from gastric and breast cancer long term survival seems possible after resection.

Adenocarcinoma↗

PubMed2001

[Effect of the learning phase on safety and efficiency of laparoscopic fundoplication].

The introduction of laparoscopic techniques into surgical practice has required a learning process on the part of the surgeons involved. The duration, morbidity, and functional outcome of laparoscopic fundoplication were evaluated in our institution's first 146 cases. During a 34-month period the patients underwent laparoscopic Nissen (n = 102) or Toupet (n = 44) fundoplication. Conversion to open access was necessary in 7 cases, re-operation for complications in 2, all among the first 40 cases of the series. The median operating time was 165 min (range 75-375) in the first 40 cases, and 105 min (range 50-235) thereafter (P < 0.001). Body mass index, grade of esophagitis, and the surgeon's experience were independent predictors of the operating time. One hundred and thirty-four patients (92%) could be evaluated for recurrence of reflux, which was encountered in 2 (5%) of the first 40 cases and 8 (8%) of 94 patients in the later group.

Adult↗

PubMed2001

[Staged resection in rectal carcinoma].

INTRODUCTION: The objectives of surgical treatment of rectal cancer are radical tumor excision, low morbidity and adequate functional outcome. The technique of total mesorectal excision (TME) has reduced the rate of local recurrences and led to an increase of ultra-low colorectal and coloanal anastomoses, which have a higher risk for anastomotic leakage. METHODS: Advantages, disadvantages and consequences of staged resection for rectal cancer are discussed on the basis of international literature and our own results. RESULTS: There are few stringent criteria for the use of diverting stomas. The decision for staged resection is often influenced by the personal experience of the surgeon. CONCLUSIONS: The occurrence of anastomotic leaks cannot be prevented by diverting ostomies, but the usually irreversible consequences regarding survival and functional outcome can be minimized.

Anastomosis, Surgical↗

PubMed2001

Contralateral breast cancer: molecular differentiation between metastasis and second primary cancer.

Previous cancer in one breast is a strong known risk factor for cancer in the contralateral breast. Differences in tumor histology and nuclear grading are applied to distinguish between a metastatic spread and a second primary cancer, although cancers of the breast often share the same histological features. Comparison of genetic alterations in paired tumors may provide the most reliable approach for discerning clonal relationships, hence uncovering the presence or absence of multiple primary cancers. We compared tumors from 33 patients with cancer in both breasts for mutations in the p53 gene. With this molecular approach, we were able to define the relationship within paired tumors in 13 patients. The paired tumors of two patients shared the same mutation, revealing the second lesion in one case as a contralateral metachronous lymph node metastasis appearing 29 months after first surgery, and in the other as a spread to the opposite breast. In 11 patients, mutations were either discordant or solely present in one of the lesions, confirming the diagnosis of bilateral breast cancer. Histopathological evaluation had failed to provide firm diagnosis in nine out of 11 instances on account of concordances in pathological parameters such as histological type and grading. In our study, we could show that bilateral breast malignancies most frequently represent two primary breast cancers. We could also demonstrate that contralateral breast cancer spread does occur. Standard pathological assessment allowed a firm diagnosis only in the presence of different histological types.

Adult↗

PubMed2001

Unexpected severe myelotoxicity of gemcitabine in pretreated breast cancer patients.

Gemcitabine is a chemotherapeutic agent with proven antitumor effects in pancreatic and non-small cell lung cancer; however, studies establishing the definite significance in other solid tumors are still in progress. We herein present three female patients with advanced breast cancer who received gemcitabine as salvage chemotherapy. Gemcitabine at a dose of 1250 mg/m2 was scheduled for days 1, 8 and 15 with a subsequent rest for 1 week. However, within 1 week after the very first administration of gemcitabine myelotoxicity WHO grade IV occurred in all patients, leading to discontinuation of therapy. In two patients this gemcitabine-induced hematotoxicity could be overcome by means of vigorous supportive care, but one patient died after cerebral bleeding due to severe thrombocytopenia. We conclude that gemcitabine in heavily pretreated breast cancer patients should only be used with extreme caution with special focus on platelet counts until solid data from clinical studies for doses and schedules are available.

Adult↗

PubMed2001

Evaluation of the United States Food and Drug Administration-approved scoring and test system of HER-2 protein expression in breast cancer.

PURPOSE: The purpose of this study was to investigate the prognostic significance of assessment of human epidermal growth factor receptor (HER)-2 oncogene protein overexpression of breast cancer tissue by the United States Food and Drug Administration (FDA)-approved HercepTest and grading system (negative, 0 or 1+; weakly positive, 2+; strongly positive, 3+). Furthermore, results of the HercepTest were correlated with immunohistochemical results obtained using different antibodies and protocols and with HER-2 oncogene gene amplification assessed by fluorescence in situ hybridization (FISH). EXPERIMENTAL DESIGN: HER-2 status in 303 patients with lymph node-positive breast cancer was investigated by using a rabbit polyclonal antibody (DAKO) by conventional immunohistochemistry and by applying the HercepTest. Furthermore, the monoclonal antibody CB-11 was used in conventional immunohistochemistry and with the NexES automatic stainer, which is also under consideration for FDA approval for determination of eligibility for Herceptin therapy. Results were compared with FISH analysis performed in all 2+ and 3+ specimens (103 cases) and 104 HER-2-negative specimens. RESULTS: 3+ positive carcinomas were found in 8.9-15.7% of specimens. FISH revealed that almost exclusively 3+ positive cases were amplified, with the HercepTest and the NexES automatic stainer giving the best results. In univariate analysis, staining with the HercepTest revealed a significantly worse prognosis in 3+ cases. Also, 3+ cases were significantly associated with lower estrogen receptor levels and histological grade III tumors. CONCLUSIONS: This study shows that the results of the FDA-approved HER-2 grading and test system correlated strongly with findings in FISH. Furthermore, HercepTest proved to be of prognostic relevance. Strict adherence to the given protocols is critical.

Adult↗

PubMed2001

Efficacy and safety of thoracoscopic sympathicotomy for hyperhidrosis of the upper limb. Results of 734 sympathicotomies.

BACKGROUND: Thoracoscopic sympathicotomy (TS) evolved as treatment of choice in severe hyperhidrosis. The aim of this study was to assess the role of video-assistance in TS (VATS) versus conventional TS (CTS) for primary hyperhidrosis of the upper limb with regard to safety, side-effects and long-term outcome. METHODS: 734 TS were performed from below T1 to T4 in 406 patients. In the CTS and in the VATS group 558 and 176 procedures were performed, respectively. Follow-up was completed in 82% of all patients after a median observation period of 16 years. RESULTS: Dry limbs were immediately achieved in 92% (CTS) and 97% (VATS, p = 0.98). Only one patient (CTS) underwent conversion due to bleeding. In the CTS group Horner's syndrome occurred in 2.2% and rhinitis in 9.9% of procedures. No patient of the VATS group experienced Horner's syndrome (p = 0.025), 3 patients developed rhinitis (p = 0.11). At follow-up compensatory sweating was observed in 67.6% vs. 55.6% (p = 0.051) and gustatory sweating in 50.4% and 33.3% (p = 0.01). There were 5 failures or recurrences (1.9%) in the CTS group and 2 (2.8; p > 0.05) in the VATS group at reevaluation. Overall 6.5% (CTS) and 5.6% (VATS) of patients regret the operation (p = 0.7). CONCLUSIONS: We observed a significant decrease of the incidence of complete or incomplete Horner's syndrome and gustatory sweating when the procedure was guided by video-imaging while success rate was similar when compared with CTS.

Adult↗

PubMed2001

Prognostic relevance of three histological grading methods in breast cancer.

Histological grading is an important parameter for the risk assessment in patients with breast cancer. However, up to now differing grading methods are used which have not been compared with respect to their prognostic significance. In the present study the prognostic significance of three different methods of histological grading (Elston, Contesso, Helpap) was determined in a sample of 292 patients. Furthermore, results obtained in needle biopsies were compared with those obtained in surgical resection specimens in 31 cases. The mitotic counts and the Contesso method were performed on two microscopes with different field areas (0.238 mm2 and 0.345 mm2). Univariate and multivariate analysis revealed that all three histological grading methods had a high prognostic value concerning overall survival (OS) and disease-free survival (DFS). Using univariate and multivariate analysis the Elston method performed best to determine OS and DFS (p<0.0001 and p<0.001). The field area of the microscope had a minor influence on the mitotic count and on the results of the Contesso method. The histological grading was reliable in needle biopsies: the best agreement to grading obtained in the definitive surgical specimen was achieved with the Elston method (kappa statistic 0.727). As a conclusion, we could show that determination of the histological grade is an important prognostic factor in breast cancer with the Elston method giving the best results. Also, we could demonstrate that histological grading in needle biopsies is reliable enough to allow a preoperative risk estimation.

Austria↗

PubMed2000

[Status of surgical studies in oncology. I].

Advances in surgery, anesthesiology and in critical care remarkably elevated safety of surgical therapy of cancer. However, prognosis of most cancer types as esophageal and gastric carcinoma--as discussed in this part of the survey--did not improve, even not after adjuvant therapy. To enhance curative resection rate chemotherapy and radiation or a combination of both have been performed preoperatively. The weakness of radiotherapy is control of distant metastases, chemotherapy failed in local tumor control. Multimodal preoperative strategies offered enhanced survival in responders, but overall there was no significant survival advantage. Until now neither in esophageal nor in gastric cancer randomised studies could demonstrate a substantial overall survival benefit after extended lymphadenectomy.

Chemotherapy, Adjuvant↗

PubMed2000

[Status of surgical studies in oncology. II].

Recent prospective randomised trials dealt with the optimal extent of surgical resection as well as with preoperative therapy modalities in pancreatic, rectal and breast cancer. In pancreatic cancer extended lymphadenectomy did not improve overall survival. Total mesorectal excision remarkably changed surgery for rectal cancer. Rate of local recurrence of rectal cancer could be significantly reduced by preoperative irradiation. In advanced rectal cancers curative resection and sphincter preservation seems possible due to multimodal preoperative therapy. It has been demonstrated that in appropriate cases breast-preserving resection is comparable to mastectomy with respect to overall survival. Up to now it is not quite clear if sentinel node sampling is equivalent to routine lymphadenectomy. Following neoadjuvant chemotherapy breast-preservation rate is significantly higher, but survival is not significantly increased.

Adult↗

PubMed2000

Long-term results after laparoscopic unroofing of solitary symptomatic congenital liver cysts.

BACKGROUND: Reports about laparoscopic management of symptomatic nonparasitic liver cysts are increasing, proving the procedure feasible and safe. However, late results of endoscopic unroofing currently are not available. The primary aim of the study was to offer long-term results with a follow-up of more than 5 years. Two diagnostic pitfalls are presented. METHODS: Preoperatively, diagnosis was established by sonography, computed tomography (CT) scan, echinococcus serology, and tumor-marker measurement. The outcome of 12 laparoscopic fenestrations in 11 patients with symptomatic solitary liver cysts is presented. Nine patients were reexamined after a median observation time of 3.1 years (range, 0.6-6.4 years) by clinical investigation and ultrasonography, CT scan, or magnetic resonance imaging (MRI), respectively. RESULTS: All operations could be finished laparoscopically, and no death occurred. Simultaneous cholecystectomy was performed in six cases. All patients experienced immediate relief of symptoms. Postoperatively, no complications were observed except one patient with unilateral brachial vein thrombosis. Histologically, we discovered one hydatide cyst and one cystadenoma underlying the cystic disorder leading to further therapy. At follow-up, one of the remaining seven patients (14.3%) suffered symptomatic recurrence and successfully underwent reoperation endoscopically. CONCLUSIONS: The results of this study confirm the outcome reported previously after short- and intermediate-term follow-up showing that laparoscopic management of symptomatic solitary nonparasitic liver cysts is permanently successful in a large majority of cases when diagnosis is correct.

Adult↗

PubMed2000

Paclitaxel-containing high-dose chemotherapy in high-risk breast cancer patients.

Despite standard-dose adjuvant chemotherapy, the prognosis for patients with breast cancer and extensive axillary lymph node involvement at diagnosis is poor. The efficacy of a paclitaxel-containing, high-dose chemotherapy protocol in 21 high-risk breast cancer patients is assessed. After standard-dose chemotherapy followed by peripheral blood stem cell (PBSC) mobilization, high-dose therapy with paclitaxel, carboplatin, and cyclophosphamide and CD34-selected PBSC rescue was given. Hematologic reconstitution after high-dose therapy was rapid. Main toxicity included diarrhea grade I or II in about half of the patients and infections were observed in 19%. Five-year probabilities for relapse and failure-free survival were 32% and 62%, respectively. High-dose consolidation with paclitaxel, carboplatin, and cyclophosphamide achieves a high failure-free survival in patients with high-risk breast cancer with acceptable toxicities and stable, long-term hematopoietic reconstitution. Evaluation of the benefit of high-dose therapy in these patients in larger prospective, randomized trials is warranted and currently under way.

Adult↗

PubMed2000

Severe acute pancreatitis causes alterations in HLA-DR and CD14 expression on peripheral blood monocytes independently of surgical treatment.

OBJECTIVE: To find out if the severity of acute pancreatitis or the surgical treatment of severe acute pancreatitis influences HLA-DR and CD14 expression on peripheral blood monocytes. DESIGN: Prospective open study. SETTING: University hospital, Austria. SUBJECTS: 9 consecutive patients with severe acute pancreatitis in need of operative treatment, 5 patients with mild acute pancreatitis, and 7 healthy volunteers. INTERVENTIONS: Samples of 5 ml blood were taken daily into endotoxin free tubes at same time points. Surgical treatment for severe acute pancreatitis consisted of blunt necrosectomy, operative lavage, laparostomy, and open drainage. MAIN OUTCOME MEASURES: Correlation between HLA-DR and CD14 expression on peripheral blood monocytes on the one hand and the severity of acute pancreatitis and operative treatment of severe acute pancreatitis, on the other. RESULTS: In patients with severe acute pancreatitis expression of HLA-DR and CD14 was significantly downregulated both before and after operation (p < 0.0001; ANOVA), compared with patients with mild acute pancreatitis or healthy controls. However the expression of the two cell surface markers was not affected either by the first operation, or by the reoperations. CONCLUSION: These findings suggest that in acute pancreatitis the expression of cell surface markers on peripheral blood monocytes is related to the severity of disease but is not influenced by operative treatment.

Adult↗

PubMed2000

Tumor antigen pulsed dendritic cells enhance the cytolytic activity of tumor infiltrating lymphocytes in human hepatocellular cancer.

OBJECTIVE: Tumor infiltrating lymphocytes (TILs) stimulated with interleukin-2 (IL-2) ex vivo have been successfully used therapeutically in some cancer patients, but their potency in eliciting an effective anti-tumor response is variable. We have tried to augment killing activity of tumor infiltrating lymphocytes derived from hepato-cellular carcinoma (HCC) using autologous monocytes derived dendritic cells. METHODS: Tumor infiltrating lymphocytes (TILs) from 6 patient with hepatocellular carcinoma were isolated and the phenotype were further characterized. From the same patients, autologous dendritic cells were generated from CD14+ monocytes that were cultured for 6 days in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4). Those professional antigen presenting cells were pulsed with whole autologous hepatoma tumor lysates (pDC). TILs were cocultured with pDC or unpulsed DC. To assess the cytotoxic potency of TILs, the ability to lyse the tumor cell targets K652, Daudi and an allogeneic HCC celline was determined in a standard cytotoxic assay. RESULTS: Tumor cells targets in vitro are poorly lysed by tumor infiltrating lymphocytes indicating T-cell hyporesponsiveness. In contrast, the killing activity of HCC derived TILs against Daudi (9.15% +/- 7.5) and allogeneic HCC tumor target (18.2% +/- 9.2) could be significantly augmented when stimulated with pDC (Daudi: 38% +/- 6.8 and allogeneic HCC: 55% +/- 10). The killing activity of TILs against K562 was unaffected by pDC. CONCLUSION: The low cytotoxic activity profile of HCC derived TILs in vitro can be increased by tumor lysate pulsed dendritic cells and may therefore be more effective in vivo when used for adoptive immunotherapy.

Antigens, Neoplasm↗

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↗

PubMed2000

Primary small bowel malignancies: single-center results of three decades.

We highlight one medical center's experiences with primary malignancies of the small bowel. During a 27-year period, 79 patients were treated for small bowel tumors. Of these, 15 (20%) were lost to follow-up; thus, 64 patients were reviewed retrospectively with emphasis on histological distribution and their topography, perioperative complications, overall survival, and prognostic factors. In our 64-patient series, 33 (51.6%) presented with adenocarcinoma; 10 (15.5%), lymphoma; 8 (12.1%), leiomyosarcoma; 5 (7.6%), neurogenic tumor; 2 (3%), unclassified carcinoma; 5 (7.6%), other types of sarcoma; and 1 patient presented with synchronous adenocarcinoma and lymphoma. Of all patients, 30 (46.9%) were curatively treated, whereas 34 (53.1%) underwent palliative procedures. Hospital lethality was 9.4% and mainly occurred in patients operated on under emergency circumstances. Reoperation rate was 29.7%. The observation period lasted at least five years or until death; three patients were alive less than five years postoperatively. Cumulative five-year survival rate was 22.5% in the adenocarcinoma group, 33.3% in the lymphoma group, 33.3% in the leiomyosarcoma group, and 22.2% in patients with other tumors. The uncharacteristic symptoms presented by patients suffering from small intestinal malignancies make early diagnosis difficult. Therefore, especially in patients with long-standing bowel diseases, malignancy should be considered. Early diagnosis and surgical treatment lead to a good prognosis as shown by our study.

Adenocarcinoma↗

PubMed2000

Candida infection of local necrosis in severe acute pancreatitis is associated with increased mortality.

The aim of this study was to evaluate the frequency of Candida infection of pancreatic necrosis in patients suffering from severe acute pancreatitis (SAP) and to analyze its impact on the outcome. Two-hundred and fifty consecutive patients with SAP from January 1986 to December 1998 were studied retrospectively. Their mean APACHE II score at the day of admission was in 16.1 (range 8-35). All patients were in need of operative therapy. Overall mortality was 38.8% (97 patients). One-hundred and eighty-two patients (72.8%) suffered from local infected necrosis. Among these patients, local Candida infection was observed in 31 patients, whereof 23 patients (74%) suffered from local fungal infection detected at first operation. During the course of disease, 12 patients (39%) also revealed fungemia. Local Candida infection as compared to no Candida infection was associated with an increased mortality rate (84% vs. 32%; P 0.0001). Multivariate logistic regression analysis identified APACHE II score (P < 0.0001), age of the patient (P < 0.003), extent of pancreatic necrosis (P < 0.002), and local bacterial (P < 0.04) and fungal infection (P < 0.004) as independent factors significantly contributing to mortality. SAP, requiring surgical treatment, is associated with high in-hospital mortality. Patients suffering from local Candida infection are at high risk of fatal outcome.

Adolescent↗

PubMed2000

TP53 mutation and p53 overexpression for prediction of response to neoadjuvant treatment in breast cancer patients.

The value of p53 to predict the cytotoxic effect of two commonly used chemotherapy regimens was assessed in patients with advanced breast cancer. Response to a DNA-damaging combination therapy [fluorouracil, epirubicin, cyclophosphamide (FEC] considered to induce p53-dependent apoptosis was compared with a microtubule stabilizing therapy (paclitaxel) expected to be independent of p53 function. The p53 status of the patients' breast tumors was assessed using both immunohistochemistry (IHC) and direct sequencing of the entire p53 gene. p53 findings were correlated with treatment response, and linkage between p53 function and cellular response was assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. In a series of 67 breast tumors, 19% had TP53 gene mutations, 40% had a positive p53 IHC, and 12% had both. In the FEC group, treatment failure was related to both the presence of TP53 gene mutations (P = 0.0029) and a positive IHC (P < 0.0001). Apoptosis was almost exclusively found in tumors having normal p53 in both parameters (P < 0.0001). In the paclitaxel group, treatment response was neither related to apoptosis nor to normal p53. Combination of sequencing and IHC results revealed a significant association between abnormal p53 and response to paclitaxel (P = 0.011). We found TP53 mutations, as well as p53 protein overexpression, to be associated with response to chemotherapy. Whereas clinical response to FEC was found to be dependent on normal p53, the cytotoxicity of paclitaxel was related to defective p53. The efficiency of paclitaxel during mitosis might be supported by lack of G1 arrest due to p53 deficiency. Therefore, patients with p53-deficient tumors may benefit from paclitaxel.

Antineoplastic Agents, Phytogenic↗