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C Schuhmacher

Publications and source records attributed to C Schuhmacher.

15 recordsLinked to original sources
PubMed2001

Highly specific tumor binding of a 213Bi-labeled monoclonal antibody against mutant E-cadherin suggests its usefulness for locoregional alpha-radioimmunotherapy of diffuse-type gastric cancer.

A monoclonal antibody (E-cadherin delta 9-1) directed against a characteristic E-cadherin mutation (in-frame deletion of exon 9), found in diffuse-type gastric cancer but not in any normal tissue, was conjugated with the high linear energy transfer alpha-emitter 213Bi and tested for its binding specificity in s.c. and i.p. nude mice tumor models. After intratumoral application in s.c. tumors expressing mutant E-cadherin, the 213Bi-labeled antibody was specifically retained at the injection site as shown by autoradiography. After injection into the peritoneal cavity, uptake in small i.p. tumor nodules expressing mutant E-cadherin was 17-fold higher than in tumor nodules expressing wild-type E-cadherin (62% injected dose/g versus 3.7% injected dose/g). 78% of the total activity in the ascites fluid was bound to free tumor cells expressing mutant E-cadherin, whereas in control cells, binding was only 18%. The selective binding of the 213Bi-labeled, mutation-specific monoclonal antibody E-cadherin delta 9-1 suggests that it will be successful for alpha-radioimmunotherapy of disseminated tumors after locoregional application.

Animals↗
PubMed2001

[Therapeutic modalities and prognosis].

The individual prognosis of a patient with gastrointestinal cancer is determined by a number of clinical and biological factors. The most relevant prognostic factors are those that can be influenced by the surgeon himself. The completeness of tumor resection, the so-called residual tumor status on the level of the primary tumor in all three dimensions and on the level of the lymphatic drainge is the outstanding factor with an independent influence on the survival of the patient. In addition, the principles of blood-saving preparation with avoidance of blood transfutions, the consideration of no-touch isolation and the complication-free postoperative course have been shown to be independent prognostic factors that can be influenced by the surgeon. There is clear evidence that the hospital volume and the experience of the surgeons, expressed by the number of cases (caseload) in a specific field, has a strong impact on the outcome of a surgical treatment in gastrointestinal cancer patients. To optimize the prognosis of a patient with gastrointestinal cancer one should consider all therapy-related prognostic factors, and therapeutic modalities should be scheduled after a consensus conference (tumor board) of all therapeutic fields involved in the treatment of cancer.

Cancer Care Facilities↗
PubMed2000

Fibrovascular esophageal polyp as a diagnostic challenge.

Fibrovascular polyps are rare benign esophageal tumors that usually arise from the proximal third of the esophagus. We present the case of a 48-year-old man with a history of dysphagia and 7-kg weight loss over a period of 2 months. A barium swallow showed a distended esophagus with a tumor extending from the upper esophageal sphincter to the cardia. On a thoracic computed tomographic scan, a homogeneous intramural mass with a density of 22 Hounsfield units was seen, which extended throughout the entire esophagus. Fiberoptic endoscopy confirmed the presence an intramural tumor beginning at the upper esophageal sphincter and reaching to the cardia. The tumor was completely covered with mucosa, except for an ulcerated area at its distal end, which herniated into the stomach. On endoscopic ultrasound, the tumor appeared to grow submucosally and to respect the muscularis propria. Endoscopic biopsies from the ulcerated distal aspect of the tumor suggested a leiomyoma. None of the imaging modalities used revealed evidence of a polyp or intraluminal esophageal tumor. Rather, a potentially malignant extensive intramural tumor was suspected, and an esophagectomy was performed. Only at the time of removal of the specimen did it become evident that the tumor mass was located intraluminally with a pedicle in the region of the upper esophageal sphincter. The final pathological diagnosis was a giant fibrovascular polyp of the esophagus.

Diagnostic Imaging↗
PubMed2000

[Preoperative downstaging in advanced stomach carcinoma. Wishful thinking or reality].

By the time it is diagnosed, gastric carcinoma is usually already advanced and, as a result, has a poor prognosis. Surgery, with complete (R0) resection of the tumor, is the only chance of cure for this disease. However, in locally advanced gastric carcinoma this is only possible in approximately half of all cases. In order to help improve the prognosis of patients with advanced stage carcinomas, the concept of multimodal therapy is presently being evaluated. The results of studies of postoperative adjuvant therapy have been contradictory, with the result that no indication for such treatment outside of study protocols presently exists. Recently, preoperative application of chemotherapy, the so-called "neoadjuvant" therapy concept, has become increasingly important, since it has been demonstrated that, in individual cases, tumors thought to be primarily unresectable have been able to be completely resected after chemotherapy. Based on the available studies, one can assume that, in a subgroup of patients with not yet identified favorable tumor biologic characteristics, a true down staging of the tumor occurs. To what extent a preoperative "over-staging" may be a factor can only be estimated statistically, since the presently available methods for clinical estimation of tumor stage are never as accurate as the final histopathologic evaluation. Since the recently started, randomized multicenter study under the auspices of the EORTC compares surgery alone with a combination of surgery and preoperative chemotherapy in locally advanced gastric carcinoma, information will soon be available which will help clarify the effectiveness of this therapy concept.

Gastrectomy↗
PubMed1999

[Intestinal pouches: gastric reconstruction].

Reconstruction of the intestinal passage after a total gastrectomy is usually based on a direct esophagojejunostomy with end-to-side implantation of the afferent loop. The second principle of reconstruction is based on preservation of the duodenal passage. Long-term problems such as weight loss and malnutrition are further considerations that lead to the concept that gastric reconstruction should have the form of a reservoir. In addition to the construction of the reservoir itself, the clinical concern of avoiding gastroesophageal reflux is a further requirement for the choice of reconstruction type. Diversion of the duodenal content via a Roux-en-Y end-to-side anastomosis is considered to be the standard procedure. Interposition of a sufficiently long duodenal loop with maintenance of the duodenal passage also has the effect of preventing duodenal reflux. A theoretical advantage of this procedure is the linking of the motility of the duodenum with that of the interposed segment with improved synchronization of the aboral nutrient passage. When one considers complicated reconstructive procedures, the present literature suggests construction of a pouch is definitely functionally superior to the simple esophagojejunostomy. Whether the duodenal passage should be maintained or whether a Roux-Y technique should be used is a question that is still open for discussion.

Anastomosis, Roux-en-Y↗
PubMed1999

Loss of immunohistochemical E-cadherin expression in colon cancer is not due to structural gene alterations.

E-cadherin, a transmembrane cell adhesion molecule, has been observed to have an altered pattern of immunoreactivity in several types of carcinomas. In lobular breast cancer, loss of immunoreactivity has been shown to be due either to out-of-frame deletions or to nonsense mutations of the E-cadherin gene. We analysed 29 cases of completely resected colon carcinoma with immunohistochemistry using the HEC-D1 antibody. Normal protein expression similar to that in the adjacent nonmalignant mucosa was seen in 6 cases, whereas 23 tumours had reduced or absent E-cadherin expression. In the 8 cases with no expression of E-cadherin revealed by immunohistochemistry, the entire E-cadherin cDNA sequence was analysed. In these cases, sequence analysis failed to reveal any cDNA mutations despite the negative immunohistochemistry. Possible explanations for this discrepancy include regulatory defects in the E-cadherin promoter, abnormalities at the translation or protein processing levels and mutations in other parts of the gene that were not investigated by the cDNA analysis (e.g. intronic sequences), which could play a role in causing abnormal processing of the E-cadherin protein.

Adult↗
PubMed1999

Analysis of E-cadherin in diffuse-type gastric cancer using a mutation-specific monoclonal antibody.

In-frame deletions from the E-cadherin mRNA, coding for a homophilic cell adhesion molecule, are characteristic for diffuse-type gastric carcinomas. Using immunohistochemical analysis the mutant form cannot be distinguished from normal E-cadherin, making results difficult to interpret. In this study, a rat monoclonal antibody, designated E-cad delta 9-1, was generated against a peptide spanning the fusion junction region between exons 8 and 10. This new epitope is present in an E-cadherin variant that lacks exon 9 from the mRNA due to different splice-site gene mutations. Using Western blotting and immunohistochemistry of E-cadherin-transfected cells, we demonstrate that E-cad delta 9-1 specifically reacts with E-cadherin lacking exon 9 but not with the wild-type protein. No immunoreactivity was observed in 31 nontumorous and embryonal tissues analyzed. In gastric carcinoma specimens known to express mutant E-cadherin mRNA lacking exon 9, E-cad delta 9-1 targets exclusively tumor cells in routine formalin-fixed and paraffin-embedded material from biopsies, primary tumors, and lymph node metastases. In a retrospective series of 172 diffuse-type gastric carcinomas expressing E-cadherin, E-cad delta 9-1 reacted with 22 tumors (13%). This new tumor marker-monoclonal antibody system could open novel avenues for selective diagnosis and specific therapy of a subgroup of diffuse-type gastric cancer patients.

Animals↗
PubMed1999

Rapid detection of mutated E-cadherin in peritoneal lavage specimens from patients with diffuse-type gastric carcinoma.

Tumor cells in abdominal lavage specimens from patients with gastric carcinoma strongly predict subsequent peritoneal metastasis and poor prognosis. Reverse transcription (RT)-polymerase chain reaction (PCR) detection of wild-type E-cadherin has been claimed to be superior to conventional cytology for the detection of patients who subsequently develop peritoneal metastases. The present study tested this hypothesis and determined whether or not the detection of mutated, tumor-specific E-cadherin messenger RNA in abdominal lavage specimens serve as a useful diagnostic tool. Preoperative lavage specimens from 52 patients with diffuse-type gastric carcinoma and from 5 patients with benign disease were analyzed by conventional cytology and by RT-PCR for amplification of E-cadherin. Tumor cells were detected by cytology in 8 (15.3%) of the 52 patients with gastric cancer. The E-cadherin was detected in all 57 samples by RT-PCR. Two of these had abnormal E-cadherin amplification products confirmed to be mutations by direct sequencing, which were identical in the primary tumors. These findings suggest that the detection of wild-type E-cadherin is not sufficiently tumor specific. Also, for diffuse gastric carcinomas with confirmed E-cadherin mutations, detection of mutant E-cadherin by RT-PCR is a potentially valuable method for tumor cell detection in lavage specimens.

Ascitic Fluid↗
PubMed1998

[The German EORTC Study of neoadjuvant therapy of stomach carcinoma].

The improvement of the prognosis of gastric cancer after neoadjuvant therapy was shown in a phase II study with etoposide, adriamycin and cisplatinum (EAP). Due to high-grade toxicity with EAP, the verification of this therapeutic concept in a randomized phase III study with a less toxic regimen had to be demonstrated in a second phase II study. A combination with cisplatinum, leucovorin and 5-FU in comparison to EAP was less toxic, but clinical response after chemotherapy was shown to be identical. Of 41 patients, 36 patients underwent surgery with a R0-resection rate of 73.2% (n = 26). After a median follow-up of 18.3 months, 23 patients with R0 resection were alive, 19 patients (73%) showed no evidence of recurrent disease. There was no major morbidity and no postoperative mortality observed. Thus, chemotherapy with cisplatinum, 5-FU and leucovorin seems to be suitable for a randomized multicenter trial sponsored by the EORTC. For entrance into the study the following requirements should be met: prospective diagnostic procedures including endoscopic ultrasound (EUS) and surgical laparoscopy; standardised surgery (gastrectomy with D2-lymphadenectomy): prospective histopathological work up of the resected specimen including ypTNM category, ypUICC stages and R classification; prospectively scheduled follow-up intervals. Aim of the study, including 198 patients per treatment arm with a recruitment of 3 years and a minimum follow-up of 2 years, is the verification of the positive prognostic impact of neoadjuvant chemotherapy followed by surgery compared with surgery alone in locally advanced gastric cancer (cuT 3cN1-3cM0).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

A phase II trial of paclitaxel in the treatment of recurrent or metastatic soft tissue sarcomas or bone sarcomas.

The study aimed to determine the activity and toxicity of taxol in the treatment of recurrent or metastatic soft tissue sarcomas or osteosarcomas. The major findings are that five patients had stable disease after two cycles of chemotherapy but two of these patients were subsequently removed from the study at their own request. The other three patients progressed after an additional two cycles of chemotherapy. Seven patients progressed during the first two cycles and were removed from the study. One patient completed only one cycle of therapy and was deemed inevaluable for study response. There were eight episodes of grade 3 or 4 neutropenia and two episodes of grade 3 thrombocytopenia. One patient experienced grade 3 neurological toxicity and one patient grade 3 mucositis. Two patients are currently alive with progressing disease and one patient is alive with no evidence of disease after undergoing surgery and radiotherapy. The principal conclusions are that Paclitaxel is ineffective in treating recurrent or metastatic soft tissue sarcoma and osteosarcoma. Treatment at this dose is quite myelosuppressive, but toxicity is generally manageable. Further study of this agent is not justified in this setting.

Adult↗
PubMed1995

Preoperative chemotherapy for stage III-IV gastric carcinoma: feasibility, response and outcome after complete resection.

Despite extensive resection and systematic lymphadenectomy the prognosis of patients with locally advanced gastric carcinoma remains poor. The effect of preoperative outpatient chemotherapy with etoposide, doxorubicin and cisplatin was evaluated prospectively in 30 patients who had been shown by preoperative staging (including endosonography and surgical laparoscopy) to have gastric carcinoma stages IIIA, IIIB or IV. Haematological side-effects were common and necessitated hospitalization in 13 of 30 patients. Complete clinical response to neoadjuvant therapy was observed in eight of 27 evaluable patients. Resection was performed in 27 of 30 patients, with complete macroscopic and microscopic tumour removal in 24. There were no deaths and no major morbidity following operation. On multivariate analysis complete clinical response (P < 0.01) and complete tumour resection (P < 0.01) were the major independent predictors of long-term survival after neoadjuvant chemotherapy. Actuarial survival after complete tumour removal was superior with neoadjuvant therapy compared with results in an age-, sex- and tumour stage-matched control population who had primary resection (P = 0.07). Recurrence occurred in 17 of 23 evaluable patients who had complete tumour removal, with relapse in the tumour bed or area of lymphatic drainage in 11. These data show that neoadjuvant therapy in patients with locally advanced gastric carcinoma is feasible and appears to increase the rate of complete tumour removal. More powerful and less toxic regimens are, however, required to improve the response rate and to delay or avoid recurrence after neoadjuvant chemotherapy.

Adult↗
PubMedDate not supplied

Neoadjuvant chemotherapy for gastric cancer: update.

Neoadjuvant chemotherapy has recently received increasing attention in an attempt to increase the rate of complete tumor resections, combat systemic metastases, and prolong survival in patients with gastric cancer. The available data indicate that neoadjuvant chemotherapy is feasible and does not increase postoperative morbidity and mortality. Compared to the results that can today be obtained with primary resection and lymphadenectomy, however, preoperative chemotherapy has so far failed to show a clear increase in the rate of complete tumor removal in patients with resectable gastric cancer. In patients with locally advanced or unresectable gastric cancer, preoperative chemotherapy may cause substantial reduction in locoregional tumor mass and thus increase the resection rate. This finding appears to translate into a survival benefit for those who respond to chemotherapy and have subsequent complete tumor resection. Because of severe shortcomings in the study design of the published reports, definite conclusions cannot be drawn from the available studies. Randomized controlled prospective trials are therefore clearly warranted. Exact pretherapeutic tumor staging, standardized resection and lymphadenectomy techniques, diligent evaluation of the resected specimen, and close follow-up are essential when designing these trials to identify subgroups of patients who may benefit from neoadjuvant chemotherapy for gastric carcinoma.

Chemotherapy, Adjuvant↗
PubMedDate not supplied

Sequential and/or concurrent hypofractionated radiotherapy and concurrent chemotherapy in neoadjuvant treatment of advanced adenocarcinoma of the pancreas. Outcome and patterns of failure.

BACKGROUND/AIMS: To investigate treatment outcome and patterns of failure of sequential chemotherapy (CHT) and/or concurrent hypofractionated radiotherapy (RT) and CHT followed by surgery in locally advanced non-metastatic pancreatic adenocarcinoma. METHODOLOGY: Seven patients with locally advanced but marginal resectable tumors (close contact but no signs of infiltration of the mesenteric vessels and/or vena portae) were treated with hypofractionated RT (5x3 Gy per week) and concurrent continuous infusion (300 mg/sqm/24 h, 7 days per week) of 5-fluorouracil (FU). Ten patients with locally advanced disease with radiologically suspected infiltration of the mesenteric vessels and/or v. portae were treated with 2 cycles of Cisplatin (75 mg/sqm) and Gemcitabine (2x1250 mg/sqm), and patients without tumor progression received the same concurrent RT/CHT as group 1. Four weeks after RT/CHT radical pancreatectomy was planned for patients with stable disease or remission. RESULTS: Toxicity was low in both groups, with no CTC grade 4 toxicity. In group 1, RT/CHT was completed in all patients. There was no radiological remission, but stable disease in 5 out of 7 patients. All 5 patients underwent resection of the primary tumor with a R0-resection in 3 patients. In group 2, 8 patients completed CHT and RT/CHT treatment as planned. There were 3 with partial remission. Operation was done in 4 patients, but only one R0 resection was achieved. The median survival time for all 17 patients is 13 months, with 1- and 2-year survival being 53% and 18%, respectively. Local progression was observed in 9, peritoneal seeding in 7 and distant metastasis (mostly liver and lung) in 8 patients. CONCLUSIONS: The neoadjuvant therapy could be administered with low toxicity. Results of this study warrant further investigation aiming at optimal tailoring in of this treatment approach in these two subgroups of patients.

Adenocarcinoma↗