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A Sendler

Publications and source records attributed to A Sendler.

30 records · Page 2Linked to original sources

[Surgical relevance of preoperative diagnosis of tumors of the gastrointestinal tract--decision making in esophageal, stomach, colon and rectal carcinoma].

The increasing spectrum of therapeutic options for tumors of the gastrointestinal tract has resulted in a refinement of the pretherapeutic diagnostic strategies. The diagnostic approach in surgical institutions that are focused on primary surgical resection will therefore be much less sophisticated than in institutions who propose a selective therapeutic approach based on the pretherapeutic tumor stage and prognostic parameters. Pretherapeutic assessment of the depth of tumor infiltration, i.e. the T-category, is essential because most further diagnostic and therapeutic decisions are based on this information. This can today be achieved with a high degree of accuracy by endoscopy and endoscopic ultrasonography. Early T-stages (T1-2) are usually an indication for primary surgical resection and, after exclusion of distant metastases, no further diagnostic studies are required. In patients with locally advanced esophageal, gastric or rectum tumors (T3-4) multimodal therapeutic concepts should be considered. This usually requires additional diagnostic studies. None of the available diagnostic imaging modalities today allows satisfactory pretherapeutic assessment of lymph node metastases. The assumed nodular status should therefore currently not influence therapeutic decisions. Essential is, however, the assessment of distant metastases, since the documentation of distant tumor spread will change the therapeutic approach to a palliative situation. Detailed histologic and molecular-biologic assessment of tumor characteristics is growing in importance. This not only provides therapeutically relevant information regarding tumor grading, but opens the door towards a modern molecular diagnostic approach. It can be expected that in the near future a vast amount of relevant prognostic information can be obtained from endoscopic tumor biopsies, which may soon alter our therapeutic concepts.

Colonic Neoplasms↗

Gastric Cancer.

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Antineoplastic Agents↗

Adenocarcinoma of the gastro-esophageal junction: CT for monitoring during neoadjuvant chemotherapy.

OBJECTIVE: A clinical study was performed to assess the diagnostic value of spiral CT for evaluation of response during neoadjuvant chemotherapy (CTx) in patients with adenocarcinoma of the gastro-esophageal-junction (GEJ). Results were compared to those of endoscopy. METHODS AND MATERIAL: Twenty-five patients with histologically proven adenocarcinoma of the GEJ scheduled to undergo neoadjuvant CTx were studied. Before CT examination, 1200 ml of a vanilla flavoured paraffin emulsion were applied orally to the fasting patients and 40 mg BuscopanR or 2 mg glucagon were injected i.v. for hypotonia. Iodine (100 ml) was injected automatically (3 ml/s) and the CT scan was started 10 s after complete administration of CM. For response evaluation to CTx, four standardized parameters were measured by two experienced, blinded radiologists. The results were categorized according to the WHO classification of 1981 and compared to those of endoscopy. RESULTS: In 24 of 25 patients endoscopic and computed tomographic response evaluation showed a close correlation (r = 0.96). CONCLUSION: Spiral CT with negative oral contrast agent is a suitable technique for monitoring of GEJ masses. In combination with standardized metric parameters it offers a quantitative response evaluation in patients with GEJ masses during neoadjuvant CTx.

Adenocarcinoma↗

[Abdominal recurrence after interventions on the intestines].

Local recurrences (LR) of intestinal tumors have to be divided into intra- and extraluminal LR since operative reintervention is more frequently possible in intraluminal tumor recurrences. Esophageal cancer most frequently recurs in the posterior mediastine and in the neck. In our own patients we found 16% LR following curative esophagectomy. Curative reresection is normally not possible. Palliative treatment aims to maintain the passage of food. In gastric cancer LR is most frequently seen following resection of a diffuse type carcinoma. The incidence of 7,8% in our series is low. Curative reresection was possible in 19% of extraluminal LR and in 75% of intraluminal LR. Colon carcinoma usually recurs in the abdomen. 12% of left sided primary tumors recur in the pelvis. Quite frequently extended multivisceral resections are necessary to deal with the LR. In 69% reresection was possible and in 41.5% R0-resection was achieved. As in gastric cancer intraluminal LR tend to have a better prognosis. The decision for operative reintervention has to take individual risk factors into consideration.

Abdominal Neoplasms↗

[Volumetry of abdominal tumors. Problems--feasibility].

If multimodal tumor therapy in the abdomen is to be effective, exact staging is required for which one needs precise planimetric and volumetric data. The most important indication for clinically reliable volumetric determination of tumor size in the abdominal region is monitoring liver metastases during chemotherapy. Determination of volume can be effectively realized using 3D reconstruction. Therefore, the primary data set must be complete and contiguous. The mass should be depicted strongly enhanced and free of artifacts. At present, this prerequisite can only be complied with using thin-slice spiral CT. Phantom studies have proven that a semiautomatic reconstruction algorithm is recommendable. The basic difficulties involved in volumetric determination of tumor size are the problems in differentiating active malignant mass and changes in the surrounding tissue, as well as the lack of histomorphological correlation. Possible indications for volumetry of gastrointestinal masses in the assessment of neoadjuvant therapeutic concepts are under scientific evaluation.

Abdominal Neoplasms↗

Proliferation kinetics and PCNA expression of HL-60 cells following ionizing irradiation and granulocytic differentiation.

The human promyelocytic leukaemia cell line, HL-60, was investigated with regard to proliferation and terminal differentiation following irradiation. The cells were X-irradiated and induced with 1.25% dimethyl sulfoxide (DMSO) towards the granulocytic lineage. Proliferation was measured via cell growth, clonogenicity and the bromodeoxyuridine/DNA incorporation assay. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) expression was used to discriminate cycling from non-cycling cells. The differentiation obtained was proved by testing for the immune function of the respiratory burst (NBT reduction test). The HL-60 cells studied revealed a high radiosensitivity (D0 = 0.63 Gy). After induction with DMSO, declines in cell growth, clonogenicity and PCNA positivity of the cells indicated a decrease in proliferation and an increase in differentiation. Starting on day 2 in culture, irradiation after seeding with 1 Gy accelerated the loss of the PCNA expression in induced cells (46% v. 3% PCNA-negative control cells on day 3). Induced cells gained the capability of exerting the respiratory burst, which was found to be dose-dependent radiosensitive (42%, and 12% NBT-positive cells after 1 and 2 Gy, respectively, v. 53% NBT-positive control cells on day 8). Subpopulations in the cell line were evident in all parameters investigated. We discuss the HL-60 cell, not only as a model comparable to human progenitor cells, but also as a suitable tool in radiobiological research with regard to proliferation and differentiation following ionizing irradiation.

Cell Cycle↗

Neutrophils express the high affinity receptor for IgG (Fc gamma RI, CD64) after in vivo application of recombinant human granulocyte colony-stimulating factor.

Fc receptors are important effector molecules of neutrophilic granulocytes (polymorphonuclear neutrophils [PMN]), connecting phagocytic cells and the specific immune response. Neutrophils from healthy donors express the low-affinity receptors for IgG Fc gamma RII (CD32) and Fc gamma RIII (CD16), but not the high-affinity receptor Fc gamma RI (CD64). The latter has been found on neutrophils from patients with certain bacterial infections and can be induced in vitro after incubation with interferon-gamma. We show here that neutrophils strongly express Fc gamma RI after in vivo application of recombinant human granulocyte colony-stimulating factor (rhG-CSF). PMN from patients receiving rhG-CSF displayed higher cytotoxicity against Daudi lymphoma cells in vitro compared with control patients and with healthy donors. Fab fragments against Fc gamma RII (monoclonal antibody [MoAb] IV.3) inhibited neutrophil-mediated cytotoxicity of healthy donors but not of patients during rhG-CSF therapy. Therefore, expression of Fc receptors by PMN was investigated by flow cytometry and the mean fluorescence intensity (MFI) was compared. After staining with MoAb 32.2 against Fc gamma RL, the median MFI of neutrophils from G-CSF patients (median, 4.78; range, 2.40 to 8.50; n = 5) was significantly higher (P = .002 and P = .001, respectively) than the median MFI of patients not receiving G-CSF (median, 1.23; range, 1.01 to 1.58; n = 6) and the median MFI of healthy donors (median, 1.04; range, 0.67 to 1.12; n = 6). Fc gamma RI disappeared after the discontinuing of the G-CSF injections, but was reinduced during the next treatment cycle with rhG-CSF. The high expression of Fc gamma RI during rhG-CSF therapy correlated with enhanced cytotoxicity. In vitro incubation with rhG-CSF also enhances cytotoxicity, but only minor increments in Fc gamma RI expression were observed. Thus, during in vivo application of rhG-CSF neutrophils acquire an additional potent receptor for mediating tumor cell killing in vitro by induction of the high-affinity receptor for IgG (Fc gamma RI, CD64).

Antibodies, Monoclonal↗

Human pluripotent hemopoietic colony stimulating factor: activities on human and murine cells.

Human pluripotent colony stimulating factor (Pluripoietin) was shown to act synergistically with human pluripotent alpha-like colony-stimulating activity (Pluripoietin-alpha) supporting the proliferation and differentiation of human CFU-GM progenitor cells in vitro, increasing colony size and numbers. In addition, Pluripoietin enhanced cytotoxic activity of mature human neutrophil granulocytes in an antibody-dependent cellular cytotoxicity assay. Biological activities of Pluripoietin known so far suggest great potentials for clinical use. Preclinical in vivo studies of Pluripoietin in different disease situations may be feasible in mice, because Pluripoietin is active on granulocyte precursors and on a variety of other murine cells.

Animals↗

Reaction pattern of xenografted human salivary glands in nude mice. An immunohistological and autoradiographical study.

35 specimens of human parotid gland and 37 of submandibular gland were transplanted into athymic nude mice. At distinct time intervals, from 1 day to 8 months the transplants were collected and examined. The transplanted glands were studied by light microscopy, immunohistology and autoradiography. The following changes were detectable: acute injury to the xenograft and inflammatory reaction (day 1-7), regeneration of the transplant and the beginning of adaptation to the "mouse milieu" (day 8-30), completion of adaptation (day 30 and later). The presence of the following substances was analysed: amylase, lactoferrin, secretory component, tissue polypeptide antigen (TPA). Amylase was only detected in the early transplants. Lactoferrin was seen only in the small duct system. TPA was present during all transplantation periods and was quantitatively correlated with the 3H thymidine labeling index. From our observations we can say that the salivary glands show two different reacting compartments: a large and a small duct system. The histogenesis of the xenografts, and the relationships of the changes observed to human salivary gland diseases were discussed.

Amylases↗

Preoperative staging of gastric cancer as precondition for multimodal treatment.

Preoperative staging of gastric cancer plays a crucial role every multimodal treatment protocol. At present, staging intends to be far more than evaluation of the depth of tumor infiltration into the organ wall, that is, T stage, nodular status (N category), and the presence of distant metastases (M stage) according to UICC criteria. In modern surgical oncology it includes more often the evaluation of prognostic factors such as the RAS-protein, p53 tumor suppressor gene, growth factor receptors, cell adhesion molecules, proteolytic factors, and proliferation-associated antigens. Furthermore, evaluation of nodular status is possible by sophisticated computer programs. The conventional staging of gastric cancer using endoscopy and sonography, conventional ultrasonography, computed tomography, and magnetic resonance imaging is discussed. Possible improvements of staging in oncologic centers should include surgical laparoscopy, laparoscopic ultrasonography, and meticulous evaluation of an abdominal lavage including immunohistochemical detection of free tumor cells. The most promising tumor biology-related prognostic factors in gastric cancer are briefly discussed.

Combined Modality Therapy↗

Staging gastrointestinal cancer as a precondition for multimodal treatment.

Staging gastrointestinal cancer is useful only if it has an impact on treatment. When applying modern multimodal therapies (i.e., neoadjuvant, adjuvant, or additive treatment), meticulous staging is mandatory. Preoperative staging should include all relevant prognostic factors. If possible, modern cellular biology-related parameters should also be investigated, although their validity has not yet been analyzed properly. Using such modern techniques as endoluminal ultrasonography or video-laparoscopy, a preoperative diagnostic accuracy of 85% can be achieved, providing a sound foundation for therapeutic decisions. Assessment by TNM staging (UICC) and surgical resection without residual tumor (UICC/R0) are crucial, as it has been shown by multivariate analyses that these factors have the most impact on prognosis. Postoperative staging is mainly done by pathohistologic evaluation of the surgical specimen. It is the basis for any postoperative adjuvant or additive therapy. In this paper the diagnostic methods and their validity are discussed in relation to the various gastrointestinal tumors.

Combined Modality Therapy↗