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Biomedical subjects

W Millesi

Publications and source records attributed to W Millesi.

At least 37 records · Page 2Linked to original sources

Continuous hyperfractionated accelerated radiotherapy with/without mitomycin C in head and neck cancer.

PURPOSE: To evaluate the effect of mitomycin C to an accelerated hyperfractionated radiation therapy. The aim was to test a very short schedule with/without mitomycin C (MMC) with conventional fractionation in histologically verified squamous cell carcinoma of the head and neck region. METHODS AND MATERIALS: From October 1990 to December 1996, 188 patients entered the trial. Tumors originated in the oral cavity in 54, oropharynx in 82, larynx in 20, and hypopharynx in 32 cases, respectively. Patients' stages were predominantly T3 and T4 (158/188, 84%) and most patients had lymph node metastases (144/188, 77%) at diagnosis. Only 22 patients were female, 166 were male, the median age of patients was 57 years (range 34 to 76 years). Patients were randomized to one of the following three treatment options: conventional fractionation (CF) consisting of 70 Gy in 35 fractions over 7 weeks (65 patients) or continuous hyperfractionated accelerated radiation therapy (V-CHART; 62 patients) or continuous hyperfractionated accelerated radiation therapy with 20 mg/sqm MMC on day 5 (V-CHART + MMC; 61 patients). By the accelerated regimens, the total dose of 55.3 Gy was delivered within 17 consecutive days, by 33 fractions. On day 1, a single dose of 2.5 Gy was given, from day 2 to 17 a dose of 1.65 Gy was delivered twice: the interfraction interval was 6 hours or more. RESULTS: Mucositis was very intense after accelerated therapy, most patients experiencing a grade III/IV reaction. The mucosal reaction did not differ whether MMC was administered or not. Patients treated by accelerated fractionation experienced a confluent mucosal reaction 12-14 days following start of therapy and recovered (no reaction) within 6 weeks. The skin reaction was not considered different in the three treatment groups. Those patients treated with additional chemotherapy experienced a grade III/IV hematologic toxicity in 12/61 patients. Initial complete response (CR) was recorded in 43% following CF, 58% after V-CHART, and 67% after V-CHART + MMC, respectively (p < 0.05). Actuarial survival (Kaplan-Meier) was significantly improved in the combined treated patients. Local tumor control was 28%, 32%, and 56% following CF, V-CHART, and V-CHART + MMC, respectively (p < 0.05). CONCLUSION: We conclude that our continuous hyperfractionated accelerated radiation therapy regimen is equal to conventional fractionation, suggesting that by shortening the overall treatment time from 7 weeks to 17 days a reduction in dose from 70 Gy to 55.3 Gy is possible, with maintenance of local tumor control rates. The administration of MMC to the accelerated regimen is tolerable and improves the outcome for patients significantly.

Adult↗

Magnetic cell separation for purification of human oral keratinocytes: an effective method for functional studies without prior cell subcultivation.

In studying human oral keratinocytes, it would be very helpful to obtain a pure population of cells without prior in vitro expansion. An immunomagnetic separation technique, or magnetic cell separation (MACS), was modified for efficient purification of human oral keratinocytes. Subsequent to two-step enzymatic digestion, the cell suspension was labelled with a mouse anti-CD45 (pan-leukocyte) monoclonal antibody (MoAb) to stain mononuclear cells. In a second step a rat anti-mouse antibody conjugated with colloidal superparamagnetic particles was used. Labelled cells were retained in the magnetic field of a permanent magnet on columns containing a ferromagnetic matrix. The unlabelled, unretained cells were further examined by flow cytometry analysis, enzyme-linked immunosorbent assay and polymerase chain reaction. After the MACS procedure, unretained cells showed a strong positivity for the lu-5 MoAb (as a marker for pan-cytokeratin) and were negative for anti-vimentin (to mark mesenchymal cells), for anti-CD45 MoAb and for melanocyte-detecting antibodies, thus representing pure keratinocytes (> 98%). Purified keratinocytes maintained full viability (> 91%) and functional capacities. [3H]thymidine uptake and epidermal growth factor (EGF) receptor expression were unaltered when compared with the non-separated cell population. Furthermore, interleukin-1 alpha was detected at the protein and RNA levels in keratinocytes immediately after MACS enrichment. Our findings show that MACS appears to be a useful tool for purification of oral keratinocytes and allows for further functional studies without prior subcultivation of cells.

Animals↗

Contrast-enhanced computed tomography of freely transplanted jejunal patches after surgery in the oral cavity and oropharynx.

Thirty-two patients with jejunal patches in the oral cavity and oropharynx were examined with contrast-enhanced computed tomography (CT). The morphology of the intestinal wall, the mesenteric fatty tissue, mesenteric lymph nodes and the region of the anastomosis were evaluated and correlated with clinical findings. The size and number of mesenterial lymph nodes, which were found in 16 cases, did not correlate with tumour recurrence. The benign alterations of the intestinal wall ranged from flat surfaces with no enhancement to significant enhancement with persisting folds. In cases with persisting intestinal folds, separation of tumour recurrence was achieved by identification of a typical double-layer configuration of the enhancing mucosa, and the restriction of alterations to the intestinal wall compartment. Tumour recurrences occurred at patch margins and were reliably distinguished from normal patches. For differentiation of findings, an exact localization of jejunum-patch compartments and margins with contrast-enhanced CT was, therefore, necessary.

Adult↗

Reconstruction of the floor of the mouth with a fascial radial forearm flap, prelaminated with autologous mucosa.

To circumvent the disadvantages of extraoral skin within the oral cavity and to cover mucosal defects by mucosa, we successfully prelaminated the radial forearm flap by insertion of buccal mucosa in ten patients. In a first-step operation, free grafts of buccal mucosa were fixed to the forearm fascia and covered with an alloplastic sheet, separating the mucosa grafts and the dissected fascia between and around the grafts from the overlaying subcutaneous tissue. The dimension of the alloplastic sheet in the subcutaneous pocket was chosen according to the size of the desired flap. Underneath the alloplastic sheet, the mucosal grafts merged and the mucosal surface increased by advancing of epithelial cells under in vivo culture conditions. After two months, mucosal prelamination of the distal radial forearm fascia had led to thin, pliable and resistant fasciomucosal flaps with a mucosal surface up to 7x4 cm, allowing physiological intraoral reconstruction. The preservation of skin and subcutaneous tissue of the forearm also enabled primary wound closure, reducing donor-site morbidity.

Adult↗

Preoperative stereolithographic model planning for primary reconstruction in craniomaxillofacial trauma surgery.

High precision anatomical facsimile models of the patient's skull, individually produced by stereolithography, have been used in the preoperative planning in 16 patients with acute craniomaxillofacial trauma. In late primary repair, when open reduction and internal fixation had to wait for a decrease in facial swelling or cerebral oedema, computer-aided surgery has proven to be useful in terms of facilitating anatomical reduction, minimizing surgical approaches, saving operating time and leading to improved postoperative results, which may reduce the number of secondary corrections of post-traumatic deformities.

Acrylic Resins↗

Colour stereolithography for planning complex maxillofacial tumour surgery.

High-precision anatomical facsimile models of the patients' skulls, individually produced by colour stereolithography, were used in the preoperative planning for seven patients with complex maxillofacial tumours. Selectively coloured models facilitated the management of ablative surgery and reconstructive procedures as well. The indicators for preoperative colour stereolithographic model planning concerning maxillofacial tumour surgery are discussed.

Color↗

Oral keratinocytes derived from the peritonsillar mucosa express the proinflammatory cytokine IL-6 without prior stimulation.

The aim of the present study is to examine the cytokine expression and corresponding receptor pattern of human oral mucosa-derived keratinocytes. The mRNA expression of these cytokines from isolated and purified cells was measured by a RT-PCR method, the protein production by ELISA, and the receptor expression was determined by FACS analysis. In freshly isolated oral keratinocytes, IL-1alpha, IL-1alpha receptor antagonist, IL-6, IL-8, TGF-beta, TNF-alpha, and bFGF were detectable at the protein and mRNA level, whereas PDGF and TGF-alpha were found only at the mRNA level. There were no detectable signals for IL-2 and IL-4. The cytokine production at the protein level was independent from stimulation with PMA (phorbol myristate acetate). Unstimulated commercially available and primary isolated epidermal keratinocytes showed similar cytokine pattern except a lack of IL-6. FACS analysis revealed receptor expression on oral keratinocytes for IL-1, IL-2, IL-4, IL-6, EGF, IFN-gamma, and PDGF. In addition, receptor mRNA for IL-8, TNF-alpha, FGF-2 and KGF could be detected, but not for IL-10. Our results show that human oral keratinocytes produce a cytokine panel comparable to epidermal keratinocytes. In contrast to the epidermis, IL-6 was produced by human oral keratinocytes constitutively without prior stimulation, which may indicate their active regulation role in the maintenance of the oral mucosa.

Cell Separation↗

Technetium-99m-MIBI in primary and recurrent head and neck tumors: contribution of bone SPECT image fusion.

UNLABELLED: We prospectively investigated 200 patients with the clinical suspicion for head and neck tumors. The final diagnoses were 94 primary and 56 (37 confirmed, 19 excluded) recurrent squamous cell carcinomas (SCCs), 3 primary and 7 (4 confirmed, 3 excluded) recurrent adenoid cystic carcinomas (ACCs), 6 non-Hodgkin's lymphomas, 10 distant metastases, 6 other malignancies, 10 inflammatory and 8 other nonmalignant conditions. METHODS: Bone (600 MBq 99mTc-3,3-diphosphono-1,2-propane dicarboxylic acid tetrasodium salt) and hexakis-2-methoxyisobutyl isonitrile (MIBI) (600 MBq 99mTc-MIBI) SPECT were both performed under identical conditions (triple-head gamma camera; ultra-high-resolution, parallel-hole collimators; three-dimensional postfiltering) and judged independently and after superimposition. The results were compared to the results of biopsy, surgery and CT. RESULTS: The overall sensitivity/specificity of MIBI was 90%/78% for tumor detection and 90%/95% for the identification of malignant lymph node involvement (CT: 79%/66%, respectively 90%/79%). In the subgroup of recurrent SCC and ACC the sensitivity/specificity for tumor detection was 95%/71% for MIBI versus 78%/68% for CT. The isolated assessment of bone SPECT had a sensitivity/specificity of 100%/17% for osseous tumor spread. Image fusion of MIBI and bone SPECT differentiated between regio-local bone involvement and inflammatory changes and increased the specificity of bone SPECT to 100% in primary staging. Tumor size, stage, histology and pretreatment had no statistically significant effect on tracer uptake or diagnostic utility of scintigraphy. CONCLUSION: We propose the combined 99mTc-MIBI and bone ultra-high resolution SPECT as a highly useful imaging approach in the primary and secondary staging in patients with suspected malignancies in the head and neck region. The high specificity for malignancies in the head and neck region may be used in the differential diagnosis between head and neck malignancies and inflammatory disease in patients with the accidental finding of enlarged lymph nodes and no clinical signs of a primary tumor. Image fusion with bone scanning is mandatory for the topographical orientation and increases the specificity of bone scanning to differentiate between inflammatory or malignant causes of increased bone metabolism.

Bone Neoplasms↗

[Removal of the small intestine in autologous jejunum transplantation for reconstruction of the mouth cavity is a secondary intervention with few complications].

Reconstruction after radical tumor resection in the oropharyngeal region still represents an interdisciplinary challenge. Autotransplantation of the jejunum is a popular procedure, in which the abdominal surgeon's main task is that of harvesting enteral tissue. To evaluate this technique, a careful analysis of accompanying perioperative abdominal complications was performed. Additionally, we reexamined 35 of 66 patients still living after a follow-up period of 21 (range 2-63) months on average. The perioperative mortality of 90 patients treated for oropharyngeal malignancy using the described procedure was 7.8%. None of the perioperative deaths was caused by an abdominal complication associated with enteral resection. One abdominal reoperation was performed because of abdominal wall dehiscence. For reasons not related to enteral resection, four further patients had to be relaparotomized, two of them during their hospital stay and two after leaving hospital. In five cases we observed minor complications which could be treated nonsurgically. In the follow-up reexamination we detected no abdominal late-onset complication except small incisional hernias in six cases. Finally, we concluded that despite an elevated overall operative risk in this population, complications owing to jejunal resection were comparably low. The data regarding the rate of complications classify jejunal resection as a safe procedure for reconstructive purposes in patients suffering from oropharyngeal malignancy.

Adult↗

Mucosal prelaminated flaps for physiological reconstruction of intraoral defects after tumour resection.

In order to provide vascularised mucosa for reconstruction of intraoral defects after radical tumour resection, 5 distal radial forearm flaps and 1 fibula flap were prelaminated. Prelamination was performed by fixing small, full thickness mucosa pieces onto the fascia and covering the mucosa with an alloplastic sheet as large as the future flap. The alloplastic material was a silicone sheet (n = 2), a Gore-tex sheet (n = 3) or a titanium sheet (n = 1). The mucosa and the alloplastic material were covered by the skin and subcutaneous tissue which had been elevated to expose the fascia. With the silicone and titanium sheets, the mucosa spread on the fascia and the final flaps were thin, pliable, mucus-producing and larger than the original mucosa pieces. With the Gore-tex sheets, extension of the mucosa was prevented by adhesions and the area of mucosa on the final flap was the same size as the original graft. The six prelaminated flaps were harvested after 8-10 weeks. During this time the patients had radiotherapy and chemotherapy. Preserving the skin and subcutaneous tissue reduced donor site morbidity. Six patients had intraoral defects successfully reconstructed with mucus-producing prelaminated flaps.

Adult↗

Virtual reality for orthognathic surgery: the augmented reality environment concept.

PURPOSE: The objective of this study was to apply virtual reality technology to osteotomies of the facial skeleton. MATERIALS AND METHODS: Augmented reality can be considered a hybrid of virtual and real environment spaces, which are coregistered and simultaneously visualized. Using a see-through HMD (head-mounted display) and Interventional Video Tomography intraoperatively, partial visual immersion into a patient-related virtual data space augments the surgeon's perception as shown in an experimental study and clinical applications. RESULTS: Without limiting the surgical judgment, offering continuous observation of the operating field, the presented technology additionally provides visual access to invisible data of anatomy, physiology, and function and thus guarantees unencumbered and fluent surgery. CONCLUSION: Despite current shortcomings, augmented reality technology proved to be particularly well suited for use in osteotomies of the facial skeleton.

Anatomy, Cross-Sectional↗

Clinical manifestations and diagnostic approach to metastatic cancer of the mandible.

In a 12-month period, metastatic cancer was diagnosed in eight patients. Six of them presented with pain mimicking toothache, temporomandibular joint disorders or trigeminal neuralgia, while two showed osteopenic bone lesions in the panoramic radiography, and perimandibular swelling. Anesthesia of the lower lip was the only common clinical feature. In seven of the eight patients, a whole body bone scintigraphy and single photon emission computed tomography (SPECT) of the skull in combination with a whole body and SPECT anti-granulocyte (Tc-99m MAK 250/183) bone marrow scintigraphy was performed. One patient did not have combined scintigraphy performed secondary to severe systemic illness. In six of the seven, the results were conclusive for a metastatic bone lesion. Biopsies confirmed three patients to have a previously unrecognized primary cancer, one patient to have previously unrecognized recurrent cancer, and three patients to exhibit new metastatic spread of an already diagnosed cancer. Histology revealed breast, lung, renal cancer and a malignancy of inconclusive origin. In the remaining patient, combined scintigraphy suggested osteomyelitis, yet biopsy revealed a prostate cancer metastasis with acute inflammatory cell infiltration. Thus, the scintigraphy pattern of a hot spot in the bone scan and a cold lesion in the bone marrow scintigraphy is highly suggestive of a mandibular metastasis, if accompanied by anesthesia of the lower lip.

Aged↗

Solitary plasmocytoma of the mandible--a combined approach for treatment and reconstruction.

A 44-year-old man presented with a solitary plasmocytoma in the left mandible. After neoadjuvant radiation therapy and chemotherapy, a bone marrow biopsy was taken for cryopreservation. In simulation surgery, tumour resection and primary reconstruction were planned on an individual stereolithographic 3-D skull model. Radical tumour resection and primary reconstruction using a microvascular iliac crest bone graft was performed. In case of extensive osteolysis and/or mandibular asymmetry due to tumourous bone enlargement, preoperative model planning has proved to be a useful tool for primary reconstruction. In the three-year follow up, the patient showed no recurrence of disease.

Adult↗

Remote stereotactic visualization for image-guided surgery: technical innovation.

Additional data from imaging sources using computer navigation assistance enables virtual visualization of anatomical structures in three dimensions for stereotactic navigation during an operation. Recent developments in communication technology enable the broadcasting not only of video data, but also of stereotactic navigation data via the network. By telepresence/teleconsulting, the composite images and overlapping graphics (instrument, target structure, landmark, contour) can be seen in connected clinics, with the possibility of interactive graphic assistance. In cranio-maxillofacial surgery, the first surgical teleconsultation in real time via telecommunication of stereotactic data was performed in August 1996. A patient suffering from a post-traumatic deformity following multiple comminuted midface fractures was re-osteotomized with the aid of image-guided surgery using teleconsultation: the intraoperative position achieved could be discussed with different surgeons with regard to symmetry, hard/soft tissue relationships and occlusal details, with the possibility of on-screen planning interaction and real time evaluation of the results, over a distance of 500 km.

Computer Graphics↗

Computer-aided navigation in secondary reconstruction of post-traumatic deformities of the zygoma.

Augmented reality technology was used in 5 patients for secondary reconstruction of post-traumatic unilateral deformities of the zygomaticomaxillary complex. Three electromagnetic sensors interfaced to a computer-aided navigation system (ARTMA Biomedical Inc.) were utilized. The computer navigation procedure was planned by drawing graphic lines on the CT scan at the level of the zygomatic arch, representing the outer surface of the zygoma. The desired position of the displaced zygoma was planned by mirroring from the healthy side, using a virtual mid-sagittal plane. These virtual graphics were presented intraoperatively on a TV monitor and also on the surgeon's see-through head-mounted display. Correct reduction was assumed when the virtual line representing the position of the zygoma before the osteotomy reached the virtual line defined preoperatively as the desired position. The advantages of the technique presented are that a complete exposure of the zygomatic bone is no longer necessary, and coronal and subciliary incisions may be avoided unless enophthalmos correction has to be carried out, which was in fact necessary in 2 patients. The results of zygomatic reconstruction have been satisfactory in all 5 patients.

Adult↗

Mucosal prelamination of a radial forearm flap for intraoral reconstruction.

For reconstruction of intraoral soft-tissue defects after radical resection of squamous-cell carcinomas, the microvascular jejunal patch has been a reconstructive graft option of first choice. in addition to other advantages, these jejunal grafts are able to produce mucus. In cases in which the use of jejunal grafts is contraindicated, the fasciocutaneous radial forearm flap has enlarged the spectrum of reconstructive options. A disadvantage is that mucus production will be absent, because mucosal and lining reconstruction is performed with tissue lacking mucus-providing qualities. The authors successfully prelaminated a distal radial forearm flap with buccal mucosa in five patients. Mucosal prelamination of the distal radial forearm flap enables a physiologic reconstruction with resultant mucus production, in combination with the provision of thin, pliable, and resistant flaps. The technique lowers donor-site morbidity because of the preservation of skin and subcutaneous tissue. Reconstruction with fasciomucosal, osteomyomucosal, and myomucosal flaps by this method seems feasible.

Adult↗

Myocutaneous flaps in patients with head and neck cancer retain their immunological capacities in an activated functional state.

Free/pedicled myocutaneous flaps used as functional replacement after radical dissection of advanced stage squamous cell carcinomas of the oral cavity/oropharynx were examined by immunohistochemistry (APAAP-technique). Biopsies from eight patients were taken at the time of surgery and at 3 and 5 months post-operatively. Fifteen monoclonal antibodies were used to detect surface antigens as markers of phenotypic changes of immune competent cells. In post-operative biopsies all antigens investigated increased significantly. Significantly higher numbers of CD45RO+ (P < 0.01) and CD45RA+ (P < 0.001) leukocytes were detectable. The majority of these leukocytes were TcR alpha/beta +/CD3+ T-cells, which increased in the CD4 (P < 0.05) and the CD8 (P < 0.001) subset. In addition, B-cells (P < 0.05), granulocytes (P < 0.05), NK cells (CD16+ lymphocytic cells; P < 0.05) and mature macrophages (25F9+cells; P < 0.01) were increased. Intra- and subepidermally a significantly (P < 0.01) higher number of dendritic-/Langerhans cells (CD1a+) was detectable. In post-operative biopsies, the activation-associated antigens ICAM-1, VCAM and HLA-DR were expressed on significantly more mononuclear-/endothelial cells and on keratinocytes. Our findings indicate that the myocutaneous flaps still contained cells with immunological capacities.

Aged↗

[CT and MRI of small intestine interposition after oropharyngeal tumor resection].

Freely transplanted, microvascularly anastomosed jejunal patches can be used to cover soft tissue defects in the oral cavity or oropharynx after the resection of malignant tumors. Even a patch without complications or alteration from tumor recurrence is morphologically diverse. Therefore it is difficult to distinguish between malignant and benign alterations, and knowledge of the possible morphological spectrum and the significance of an alteration is of practical interest. Computed tomography (CT; n = 30) and magnetic resonance imaging (MRI; n = 13) were used for follow-up examinations in patients who had an operative reconstruction with a jejunal patch. Three parts of a patch were differentiated with both imaging modalities: the region of the anastomosis, the mesenterial fatty tissue and the intestinal wall. The morphology of the patches correlated with clinical findings in the following cases. The patches were identified satisfactorily by CT and MRI. The appearance of patches without complications was influenced by a variable degree of fibrosis and by persistent intestinal folds. Recurrent tumors only infiltrated the margins of the patches. Destructive alterations in the patches were always less severe than those in the original orofacial soft tissue. Postoperative follow-up examinations with CT and MRI are particularly important when tumor recurrences spread under a patch, since these tumors are invisible in the clinical examinations. CT was advantageous in demonstrating osseous alterations and showed less loss of image quality in patients for whom the implantation of multiple metallic hardware during the operation had been necessary.

Adult↗