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C Wittekind

Publications and source records attributed to C Wittekind.

At least 19 recordsLinked to original sources
PubMed1998

Apoptosis, proliferation, bax, bcl-2 and p53 status prior to and after preoperative radiochemotherapy for locally advanced rectal cancer.

PURPOSE: To investigate the relationship between apoptotic cell death, proliferative activity, and the expression of apoptosis regulating proteins in rectal cancer prior to and after radiochemotherapy. MATERIALS AND METHODS: In 32 patients dispositioned to receive preoperative radiochemotherapy for locally advanced rectal carcinoma, pretherapy biopsies and the final resected specimen after radiochemotherapy were available for analyses. Apoptotic cells were identified and quantified using in situ end labeling (ISEL) technique. The expression of the bax protein was assessed immunohistochemically. Additionally, double immunostaining was performed for apoptotic cells and bax expression. The proliferative activity was determined by immunohistochemical assessment of the Ki67 (MIB-1) and the proliferating cell nuclear antigen (PCNA). p53- and bcl-2 expression was analyzed immunohistochemically. A clinical-to-pathologic downstaging after radiochemotherapy was achieved in 25 of 32 patients (78%). During follow-up, tumor recurrence was observed in six cases. In one case, no residual tumor was detected after radiochemotherapy. RESULTS: After radiochemotherapy, the apoptotic index increased significantly in almost every case examined. In contrast, the proliferative activity was significantly decreased in resected specimens as compared to biopsies. Bax immunostaining was detected in 12/31 (39%) biopsies and in 26/31 (84%) resected specimens. In the resected specimen, significantly more apoptotic cells that were bax-positive were found than in biopsies. Bcl-2 immunostaining occurred in 15/31 biopsies and 12/31 resected specimens, respectively. Tumors that were immunohistochemically negative for p53 (20/31 [65%]) generally exhibited a higher apoptotic index and a high expression level of bax than p53-positive tumors (11/31 [35%]). However, we did not find any correlation between the (pre- and post-therapeutic) rate of apoptosis or the level of bax expression and the degree of clinical-to-pathologic downstaging or the frequency of tumor recurrence. CONCLUSION: Our results indicate that radiochemotherapy is associated with an increase in bax expression and also in apoptotic cell death. The observation of higher rates of apoptosis and bax in p53-negative tumors suggests that p53 might be a possible regulating factor of apoptosis in rectal cancer.

Adult↗
PubMed1998

Classification of regional lymph node metastasis from gastric carcinoma. German Gastric Cancer Study Group.

BACKGROUND: Classification of lymph node metastasis from gastric carcinoma was based on the localization (International Union Against Cancer/American Joint Committee on Cancer [UICC/AJCC] 1992). The authors analyzed the data of the German Gastric Cancer Study (GGCS) to determine whether the number of involved lymph nodes related to the prognosis independent of their anatomic localization (UICC/AJCC 1997). METHODS: For 477 patients of the GGCS resected for cure (UICC/AJCC R0 resection) who had involved regional lymph nodes and no evidence of distant metastases, the 1992 UICC/AJCC classification was compared with the new UICC/AJCC classification (1997) based on the number of involved lymph nodes (ILN). RESULTS: Two hundred fifty-eight patients (54.1%) had 1-6 ILN, 137 patients (28.7%) had 7-15, and 82 patients (17.2%) had more than 15. When the 1992 and 1997 UICC/AJCC classifications were compared, the prognosis of patients classified as pN1 (n = 187) in the 1992 pN classification was homogeneous, whereas there was a marked lack of homogeneity among the patients classified as pN2 (n = 290). For 103 of 290 patients with 1-6 ILN, the prognosis appeared to be more favorable (5-year survival rate, 45.5%), whereas 137 of 290 patients with 7-15 ILN had an intermediate prognosis (5-year survival rate, 29.7%). Eighty-two of 290 patients had a dismal prognosis, with a 5-year survival rate of 10.4%. There was a highly significant difference in survival (P < 0.0001). Within the groups with 1-6, 7-15, and more than 15 ILN, the localization of ILN did not significantly alter the prognosis. CONCLUSIONS: The UICC/AJCC classification based on the number of involved regional lymph nodes allows for an estimation of prognosis superior to the 1992 classification. In addition, the new classification can now be applied without methodologic problems and seems more reproducible.

Carcinoma↗
PubMed1998

Efficacy of radiochemotherapy with platin derivatives compared to radiotherapy alone in organ-sparing treatment of bladder cancer.

PURPOSE: Presently, for muscle-invasive bladder cancer, radical cystectomy is considered to be the standard treatment. Bladder preservation, in the interest of quality of life, is secondary to the primary treatment goal of curing the patient. We present a 14-year multivariate analysis of prognostic factors influencing survival and bladder preservation after transurethral resection of the bladder (TURB) and radiotherapy (RT) +/- chemotherapy. METHODS AND MATERIALS: From May 1982 to May 1996, sequential cohorts of 333 patients with bladder cancer (mean age: 66 years) were treated by either RT alone (128 patients), or with platin-based concomitant radiochemotherapy (RCT, 205 patients) after TURB. Patients (282) with muscle-invasive or T1 high-risk cancers (Grade III, residual tumor after TURB, multifocality, tumor diameter > 5 cm, associated Tis or Ta, multiple recurrences or lymph node metastases), who received a minimal target dose of 45 Gy were selected for analysis (med. follow-up = 7.5 years): after October 1985, 115 patients received cisplatin (25 mg/m2) and 69 patients carboplatin (65 mg/m2) before every treatment fraction (1.8 Gy) on Days 1-5 and 29-33 of conventional fractionated RT. RESULTS: Complete remission rate was 20% (55 of 282 patients) after radical TURB, 57% (56 of 98) after TURB plus postoperative RT, and 80% (145 of 181 patients) after TURB plus RCT (85% after concomitant cisplatin and 70% after RCT plus carboplatin). These differences were significant in multivariate analysis (p = 0.003-0.05). The strongest impact on initial response had T-category (p < 0.0001) and R-status after TURB (p < 0.0003). Cause-specific survival (CSS) was 59 and 43% after 5 and 10 years; 79% of patients survived with preserved bladder. Five-year CSS after RT, RCT-Cis, and RCT-Carbo was 40, 64, and 54%, 10-year CSS 31, 48, and 27%, respectively (p = 0.04-0.045, univariate). R-status after TURB was the only independent prognostic factor for survival and bladder preservation. For relapsed patients after cystectomy, the 5- and 10-year CSS were 40 and 33%. CONCLUSIONS: TURB followed by RT/RCT is an alternative treatment option to primary cystectomy for patients with muscle-invading bladder cancer. Compared to historic controls, the addition of cisplatin or carboplatin leads to significantly more complete remissions and better survival. Survival rates are similar to those achieved by primary cystectomy and possibly even better for selected subjects, such as patients with T3b and T4 tumors. Cystectomy should be restricted to only those patients who fail after RCT.

Adult↗
PubMed1998

Sphincter preservation with chemoradiation in anal canal carcinoma: abdominoperineal resection in selected cases?

PURPOSE: This study contained herein assessed long-term results, toxicity, and prognostic variables following combined modality therapy of patients with International Union Against (Cancer Classification T1-4, N0-3, M0 squamous-cell carcinoma of the anal canal. PATIENTS AND METHODS: Between 1985 and 1996, 62 patients completed treatment with combined modality therapy. A median total dose of 50 Gy was given to the primary, perirectal, presacral, and inguinal nodes followed by a local boost in selected cases. 5-Fluorouracil was scheduled as a continuous infusion of 1,000 mg/m2 per 24 hours on days 1 to 5 and 29 to 33 and mitomycin C as a bolus of 10 mg/m2 on days 1 and 29. Routinely processed paraffin-embedded sections were stained using monoclonal antibodies for detection of proliferating cell nuclear antigen and MIB1 (Ki-67) antigen to determine the labeling index. In addition, DNA ploidy was assessed after Feulgen staining. RESULTS: Actuarial cancer-related survival, no evidence of disease survival, and colostomy-free survival rates at five years were 81, 76, and 86 percent, respectively. In univariate analysis, T category (T1/2 vs. T3/4) was predictive for no evidence of disease survival (87 vs. 59 percent; P = 0.03) and colostomy-free survival (94 vs. 73 percent; P = 0.05). N category (N0 vs. N1-3) influenced actuarial cancer-related survival (85 vs. 58 percent; P = 0.002) and no evidence of disease survival (80 vs. 53 percent; P = 0.02). A higher proliferative potential as measured by the MIB1 labeling index was associated with a better colostomy-free survival (90 vs. 50 percent; P = 0.04). In multivariate analysis, actuarial cancer-related survival was only influenced by the N category (P = 0.03) and no evidence of disease survival by N category (P = 0.03) and mitomycin C dose (P = 0.04). Salvage abdominoperineal resection achieved long-term control in only four of seven patients with local failures. CONCLUSION: Treatment with a combination of radiotherapy and chemotherapy is safe and effective for patients with anal canal carcinoma. Abdominoperineal resection is indicated as a salvage procedure in nonresponding and recurrent lesions and may be of benefit in a small subgroup of patients with poor prognostic factors.

Adult↗
PubMed1998

Prospective multicenter study of the quality of oncologic resections in patients undergoing laparoscopic colorectal surgery for cancer. The Laparoscopic Colorectal Surgery Study Group.

PURPOSE: Laparoscopic colorectal surgery for cancer is currently under discussion. Results of large, randomized studies will not be available for a number of years yet. This study analyses the results of such resections in consecutive patients operated on by unselected surgeons. METHODS: A prospective, observational, multicenter study was initiated on August 1, 1995, in the German-speaking countries of Europe. One year after initiation of the study, findings are presented with respect to the quality of oncologic resections. RESULTS: Of 500 operations, 231 (46 percent) were performed for cancer, 167 (33 percent) with a curative intent. The most common curative resections were as follows: 63 anterior rectum resections (38 percent), 51 sigmoid resections (30 percent), and 27 abdominoperineal resections (16 percent). Segmental resections were performed in 20 patients (12 percent). Intraoperative tumor spillage was reported in 2 percent. Mean number of lymph nodes harvested was 13 (confidence interval, 5-95 percent; range, 11.5-14.6) and positive lymph nodes harvested was 2.2 (confidence interval, 5-95 percent; range, 0.9-3.4). Significant differences were noted between participating centers in terms of number of lymph nodes resected (P < 0.0001). Distal and proximal resection margins were tumor-free in every case. Lateral margins were tumor free when examined. In the case of 63 curative anterior resections, the mean distal resection margin was 39 (confidence interval, 5-95 percent; range, 33-45) mm, and in 8 of these resections, it was less than 20 min. Mean blood loss was 344 (confidence interval, 5-95 percent; 292-396) ml, and 21 percent of patients received blood transfusion. CONCLUSIONS: These data document that the average quality of laparoscopic colorectal procedures for cancer is satisfactory but differs among surgeons.

Aged↗
PubMed1998

[Proliferation and apoptosis before and after preoperative simultaneous radiochemotherapy of rectal carcinomas].

PURPOSE: To investigate the relationship between apoptotic cell death, proliferative activity, and the status of the tumor suppressor gene p53 in rectal cancer before and after radiochemotherapy. MATERIALS AND METHODS: Thirty-two patients dispositioned to receive preoperative radiochemotherapy for locally advanced rectal carcinoma prior to radical surgical tumor resection were analysed. In all cases, pretherapy biopsies and the final resected specimens after radiochemotherapy were available for analyses. Apoptotic cells were identified and quantified using in situ end labeling (ISEL) technique. The proliferative activity was determined by immunohistochemical assessment of the Ki67 (MIB-1) antigen. p53 expression was analysed immunohistochemically as well. A clinical-to-pathologic downstaging after radiochemotherapy was achieved in 25/32 patients (78%). In one case, no residual tumor was detected after radiochemotherapy. RESULTS: After radiochemotherapy, the apoptotic index increased significantly in almost every case examined. In contrast, the proliferative activity was significantly decreased when comparing biopsies and resected specimens. Tumors that were immunohistochemically negative for p53 generally exhibited a higher apoptotic index than p53 positive tumors. However, we did not find any correlation between the (pre- and post-therapeutic) rate of apoptosis and the degree of clinical-to-pathologic downstaging. CONCLUSION: Our results indicate, that radiochemotherapy induces an increase in apoptotic cell death. The observation of higher rates of apoptosis in p53 negative tumors suggests that p53 might be a regular of apoptosis in rectal cancer.

Adenocarcinoma↗
PubMed1998

Improvements in staging of gastric carcinoma from using the new edition of TNM classification.

AIMS: To recognize possible advantages of the 5th edition of TNM of gastric carcinoma in comparison to the former edition. METHODS: Data from Erlangen Cancer Center for 898 patients with gastric carcinoma treated surgically by total or subtotal gastrectomy with en bloc lymphadenectomy were analysed. RESULTS: The prognostic significance of TNM has been improved by the new edition as demonstrated by the likelihood ratio test. In addition, uncertainties of method in the pathological classification of regional lymph-node metastasis inherent in the 4th edition can now be avoided. CONCLUSION: The changes in the TNM classification introduced by the 5th edition are justified by data from the Erlangen Cancer Center, have methodic advantages in determining the N classification, and lead to an improvement in estimation of outcome.

Adult↗
PubMed1998

Distribution and pharmacokinetics of Photofrin in human bile duct cancer.

Prognosis of patients with bile duct tumors is mostly poor due to late diagnosis and a lack of adequate curative and palliative treatment modalities. To evaluate the potential of photodynamic therapy (PDT) as a novel and alternative treatment approach, we have investigated the uptake and tumor-specific localization of the photosensitizer Photofrin in human biliary tract neoplasms. We have quantified the distribution and the pharmacokinetics of Photofrin in normal and tumor tissue biopsies of the human bile duct by quantitative fluorescence microscopy and digital image analysis of cryosections. Fluorescence intensities (expressed as a percentage of a standard) are 19.0 +/- 11.4% and 25.2 +/- 12.7% for tumors and 10.9 +/- 2.9% and 13.2 +/- 9.1% (mean +/- SD) for normal bile duct tissue at 24 h (n = 5) and 48 h (n = 8) after Photofrin administration (2 mg kg-1 i.v.), respectively, and decrease afterwards in normal bile duct tissue over the period of investigation (4-35 days). The ratios of fluorescence in tumor versus normal tissue are found to be 1.7 +/- 0.7 and 2.3 +/- 1.2 (mean +/- SD) at days one and two after Photofrin administration, respectively. Thus, Photofrin preferentially accumulates in bile duct neoplasms, reaching peak values during the first two days. These data suggest that laser irradiation should be performed within this period after Photofrin injection to achieve tumor selectivity of PDT for effective treatment of bile duct carcinoma.

Adenocarcinoma↗
PubMed1997

Conversion of recurrent delta-positive hepatitis B infection to seronegativity with famciclovir after liver transplantation.

BACKGROUND: Recurrent hepatitis B infection after liver transplantation is associated with poor graft and patient survival. Famciclovir is a nucleoside with virostatic action in hepatitis B infection. We report the case of a 51-year-old patient who developed recurrent delta-positive hepatitis B infection after liver transplantation. After famciclovir treatment, he became seronegative for hepatitis B early and hepatitis B surface antigens and developed protective anti-hepatitis B surface antibody titers. METHODS: After recurrent hepatitis B was confirmed, treatment with famciclovir was initiated. RESULTS: Eighteen days after starting famciclovir, the patient became seronegative for hepatitis B early antigen and delta antigen, and hepatitis B virus DNA was no longer detectable in serum. Three months later, the patient became hepatitis B surface antigen negative and remains well 16 months later with increasing anti-hepatitis B surface levels. CONCLUSIONS: Antiviral treatment with famciclovir may be useful in treatment of delta-positive hepatitis B infection following liver transplantation. Further evaluation of famciclovir in treatment and prevention of hepatitis B in these patients is warranted.

2-Aminopurine↗
PubMed1997

[Leiomyosarcoma of the esophagus. Clinical aspects, diagnosis and therapy based on an individual case].

Leiomyosarcomas of the esophagus are rare tumors of mesenchymal origin. Apropos of a case we present clinicopathological features, diagnostic procedures and management of this seldom tumor of the esophagus. Primary gastrointestinal sarcomas cause less than 0.5% of all esophageal malign tumors, and present in ca. 5% as esophageal leiomyosarcomas. The most frequent incidence ranges between the fourth and fifth decade of life. The tumors originate from the muscular layers of the esophageal wall and are localized predominantly in the middle and distal third of the esophagus. Dysphagia is the most important and leading symptom although it presents late in the course of the illness. Endosonography is at the time the most accurate method to establish the tumor size. Differentiation between leiomyoma and leiomyosarcoma is only possible by histopathological examination and may be difficult in certain cases. Histopathological grading of the tumors as low- and high-grade sarcomas in dependence of the number of mitosis affects predominantly the prognosis of these patients. Differential diagnosis includes spindle cell carcinoma and carcinosarcoma of the esophagus. The most effective therapy consists in the complete operative removal of the tumor, in these cases five years survival rates of 30 to 40% are achieved, strongly influenced by tumor differentiation and size.

Adult↗
PubMed1997

[Cronkhite-Canada syndrome. Epidemiology, symptoms, morphology and therapy based on a case report and literature review].

Juvenile polyposis was first described by Cronkhite and Canada in 1955. This disease is characterized by juvenile intestinal polyps and ectodermal abnormalities. The etiology of Cronkhite-Canada syndrome (CCS), however, is still not well understood. Interestingly among patients with CCS a significant correlation (16.5%) with intestinal carcinomas has been observed. Thus, malignant transformation and/or genetic predisposition may be involved in the initiation of the disease. In the following, epidemiology, symptoms, morphology and therapy of CCS are discussed. Our examinations are based on studies reported in the literature and on a case report of a female patient who developed a colon carcinoma 2 years after initial diagnosis of CCS.

Adenocarcinoma↗
PubMed1997

Risk of invasive carcinoma in colorectal adenomas assessed by size and site.

BACKGROUND: The risk of invasive carcinoma developing in colorectal adenomas is influenced by a number of characteristics of both patients and adenomas, and the composition of the sample analysed. PATIENTS AND METHODS: Between 1978 and 1993 more than 20,000 polyps were prospectively documented at the Erlangen Registry of Colorectal Polyps, and analysed statistically by logistic regression. RESULTS: The size of the adenomas proved to be the most important factor for adenomas equal to or larger than 15 mm as compared with smaller lesions. In 5,137 diminutive adenomas (< or = 5 mm) invasive carcinoma was never found. Adenomas in the right-sided colon had a lower risk than those in the left colon or rectum, but with increasing adenoma size, the malignancy rate showed a right-sided shift. In adenomas of up to 36 mm in diameter, invasive carcinoma was found more often when they were located in the rectum or left colon while adenomas larger than 36 mm were more likely to harbour invasive carcinoma when located in the right or left colon rather than in the rectum. CONCLUSIONS: A multivariate analysis of 11,380 adenomas detected at the first total colonoscopy showed that the factors size and site, both of which can be assessed by endoscopic inspection alone, were found to enable a statistically and clinically adequate assessment of the malignancy risk.

Adenoma↗
PubMed1997

The incidence of port-site metastases might be reduced.

BACKGROUND: Laparoscopic resection for cancer is controversial and port-site metastases are not infrequent. The mechanisms of occurrence of port-site metastases remain unclear. Animal experiments have suggested a role for carbon dioxide (CO2), but port-site metastases also occur after thoracoscopy, where no CO2 is used. The aim of this study was to define the role of CO2 in the seeding of tumor cells in the human patient. METHODS: CO2, instruments, trocars, suction device, and peritoneal washing were examined during 12 staging laparoscopies for pancreatic cancer. The presence, viability, and biological significance of cells were investigated using conventional cytology, polymerase chain reaction (PCR), and restriction fragment length polymorphisms (RFLPs) to detect the presence of a mutant k-ras gene as a genetic marker of cancer cells. RESULTS: Cytology exam of peritoneal washing, instruments, the suction device, and trocars revealed many cells. Tumor cells were detected in 6/12 peritoneal, in 4/12 trocars and 4/11 instruments washings, but not in 12 CO2 samples. The DNA content of CO2 was very low-as assessed by PCR. Mutant DNA was detected by RFLP in four out of 12 aerosols. Six aerosols did not contain any DNA. Two aerosols were borderline. CONCLUSIONS: During staging laparoscopy for pancreatic cancer in humans, CO2 contains only very low levels of free-floating tumor cells, even in the presence of massive peritoneal contamination. These results suggest that the incidence of port-site metastases might be reduced if mechanical contamination of the port sites with instruments or with the specimen can be avoided.

Adenocarcinoma↗
PubMed1997

Multiple simultaneous gastric carcinomas.

A total of 1664 patients with gastric cancer were examined to evaluate the rate of multiple synchronous primary tumours. In cases of multiple synchronous cancer (MSC), the tumours were analysed immunohistochemically for their expression pattern of p53, c-erbB2, ras, E-cadherin and proliferative activity. Multiple synchronous gastric carcinomas (MSCs) were observed in 61 out of 1664 patients (3.7%), with a total of 134 carcinomas. In our series, early carcinoma was observed more frequently in MSC than in solitary cancers. The comparison of tumour stage in MSC and solitary tumours revealed that multiple early gastric cancers were significantly more often of type I (protruded type) and IIa (superficial elevated type) than solitary early cancer. Multiple advanced carcinomas were more often of a lower pT category than solitary advanced gastric cancer. Performing immunohistochemistry for p53, c-erbB2 and ras in 134 tumours with MSCs, we observed positivity rates of 33%, 59% and 87% respectively. In 43 patients, the multiple tumours in each individual patient demonstrated an identical status of p53 and c-erbB2, and in 42 patients a similar pattern of E-cadherin expression was observed. The proliferative index, determined by proliferating cell nuclear antigen (PCNA) immunolabelling, did not differ significantly between the MSC in each patient. Ras immunostaining was detected in 53 out of 61 patients, but also in metaplasia and regenerative hyperplasia in the specimens. In survival analysis, no difference was observed between patients with solitary or multiple early or advanced carcinomas. Our results suggest that in at least a high proportion of patients with gastric cancer multiple primary tumours arise from precancerous conditions leading to similar genetic alterations.

Aged↗