[Skull base surgery in the German DRG system-New categorization of important procedures]. / Die Schädelbasischirurgie im deutschen DRG-System ­ Neue Zuordnung wichtiger Prozeduren.

Surgery of the skull base includes interventions between the nose or paranasal sinuses (anterior skull base) or ear/temporal bone (lateral skull base) and the intracranial space. As interventions at the anterior skull base almost exclusively involve complex pathologies in a demanding anatomical region, in many cases two experienced surgeons from different disciplines are required who should be experienced in operating together. The technical and time requirements are also considerable in many cases; however, for many procedures there are no specific skull base operational and procedural keys (OPS) codes that take the considerable personnel and structural effort into account. A change in the diagnosis-related groups (DRG) system, implemented since the beginning of 2023, now adjusts the remuneration of the abovementioned effort for malignant pathologies of the anterior and lateral skull base. The reallocation of procedures 5­015.0/1/3/4 and 5­016.0/2/4/6 results in a significant upgrade of anterior and lateral skull base surgery. Since the beginning of 2023 skull base surgery will no longer be charged under DRG D25C with a (former) relative weight of 1.893, but with DRG D25B with a current relative weight of 3.753 when a code of the aforementioned groups is used. Nevertheless, further adjustments are necessary, for example, in the available reconstructive steps in order to provide the Institute for the Remuneration System in Hospitals (InEK) with the most differentiated data possible on the procedural effort of the intervention and to achieve a more balanced distribution of the reimbursements of skull base surgery in the long term.

Interruption of classic CD40L-CD40 signalling but not of the novel CD40L-Mac-1 interaction limits arterial neointima formation in mice.

The co-stimulatory immune molecule CD40L figures prominently in a variety of inflammatory conditions including arterial disease. Recently, we made the surprising finding that CD40L mediates atherogenesis independently of its classic receptor CD40 via a novel interaction with the leukocyte integrin Mac-1. Here, we hypothesised that selective blockade of the CD40L-Mac-1 interaction may also retard restenosis. We induced neointima formation in C57/BL6 mice by ligation of the left carotid artery. Mice were randomised to daily intraperitoneal injections of either cM7, a small peptide selectively inhibiting the CD40L-Mac-1 interaction, scM7, a scrambled control peptide, or saline for 28 days. Interestingly, cM7-treated mice developed neointima of similar size compared with mice receiving the control peptide or saline as assessed by computer-assisted analysis of histological cross sections. These data demonstrate that the CD40L-Mac-1 interaction is not required for the development of restenosis. In contrast, CD40-deficient mice subjected to carotid ligation in parallel, developed significantly reduced neointimal lesions compared with respective wild-type controls (2872 ± 843 µm² vs 35469 ± 11870 µm²). Flow cytometry in CD40-deficient mice revealed reduced formation of platelet-granulocyte and platelet-inflammatory monocyte- aggregates. In vitro, supernatants of CD40-deficient platelet-leukocyte aggregates attenuated proliferation and increased apoptosis of smooth muscle cells. Unlike in the setting of atherosclerosis, CD40L mediates neointima formation via its classic receptor CD40 rather than via its recently described novel interaction with Mac-1. Therefore, selective targeting of CD40L-Mac-1 binding does not appear to be a favorable strategy to fight restenosis.

Percutaneous embolization of carotid paragangliomas using solely Onyx.

BACKGROUND AND PURPOSE: Paragangliomas are highly vascularized usually benign neoplasms arising from nerve tissue. Endovascular preoperative embolization is used to facilitate surgery but is often not complete, due to tiny feeding arteries not feasible for selective catheterization. Our purpose was to evaluate angiographic and clinical outcome using Onyx for percutaneous glomus tumor embolization. MATERIALS AND METHODS: A consecutive series of 4 patients with 6 paragangliomas located at the bifurcation of the common carotid artery were treated with percutaneous embolization using Onyx as the sole embolic material. RESULTS: Complete devascularization of the 6 paragangliomas was achieved using a percutaneous embolization technique with Onyx as a sole agent, combined with an endovascular microballoon that offered protection of the internal carotid artery. CONCLUSIONS: Further documentation is necessary to prove the higher grade of devascularization of paragangliomas with Onyx compared with other embolic material and the associated potential to facilitate surgery. Nevertheless, Onyx seems to be safe when used percutaneously due to its lavalike pattern flow and its controllable properties, allowing slow tumor bed penetration.

[Incidence, latency, and prognosis of local and regional recurrences in patients with upper aerodigestive tract cancer treated by laser microsurgery: influence of initial tumor parameters]. / Lokale und regionäre Rezidive von laserchirurgisch behandelten Plattenepithelkarzinomen des oberen Aerodigestivtrakts: Häufigkeit, Latenz und Prognose sowie Einfluss der initialen Tumorparameter.

INTRODUCTION: The aim of the present study is to identify clinical factors that influence the incidence and the prognosis of local and regional recurrences. PATIENTS AND METHODS: The data of 1,426 patients with newly diagnosed squamous cell carcinoma of the upper aerodigestive tract who were treated by curative laser microsurgery between August 1986 and December 2002 were reviewed. RESULTS: In 381 patients (27%), tumor recurrences were detected during follow-up. The frequency of local as well as regional recurrences significantly correlated with the initial stage of tumors. Recurrences of advanced carcinomas occurred considerably sooner than those of stage II and I cancer. During the 4th year of follow-up, patients with early stage disease had a recurrence rate twice as high as those with advanced carcinomas. Survival with recurrence was adversely affected by adjuvant radiotherapy as part of initial treatment, simultaneous local and regional manifestation of recurrence, male sex, advanced stage of initial disease, and by oral or hypopharyngeal site of the primary tumor. CONCLUSION: Early carcinomas of the upper aerodigestive tract recur at a lower rate than advanced stage diseases, but after a longer mean latency period. As a consequence, these patients should receive close follow-up also during the 3rd and 4th years after treatment, particularly as the prognosis of their recurrences is most often favorable.

Platysma myofascial flap for reconstruction of oropharyngeal defects after transoral laser microsurgery of locally advanced carcinomas.

INTRODUCTION: Transoral laser microsurgery of locally advanced carcinomas of the lateral oropharynx often results in exposure of major vessels of the neck and may be accompanied by a substantial risk of intra- and post-operative bleeding. PROCEDURE: Six patients with tonsillar cancers radiologically infiltrating the parapharyngeal space underwent ipsilateral neck dissection with temporary protection of neck vessels. While the neck remained open, transoral laser resection of the primary tumour was performed. Pharyngeal defects were subsequently closed by a superiorly based platysma myofascial flap. RESULTS: All tumours were completely resected. Intra- and post-operative bleeding complications requiring blood transfusion or surgical revision did not occur. None of the patients developed a cervical fistula. During a mean follow-up time of 24.8 months, no local and/or regional recurrence was observed. CONCLUSION: The described approach is oncologically safe and seems to ensure reliable protection of neck vessels during and after transoral laser resection of locally advanced oropharyngeal carcinomas, as well as to prevent fistula formation.

[Transoral resection of locally advanced squamous cell carcinoma of the lateral oropharynx: combination of CO2 laser microsurgery with flap reconstruction]. / Transorale Resektion lokal fortgeschrittener Plattenepithelkarzinome der Oropharynxseitenwand: Kombination der CO2-Lasermikrochirurgie mit einer primären Defektdeckung.

INTRODUCTION: Transoral laser microsurgery of locally advanced carcinomas of the lateral pharynx often results in exposure of major vessels of the neck and is accompanied by a substantial risk of intra- and postoperative bleeding. We therefore only perform these operations after external protection of neck vessels, if necessary combined with flap reconstruction. PATIENTS AND METHODS: Between October 2001 and December 2004, 11 locally advanced squamous cell carcinomas of the lateral oropharynx that reached the major vessels of the neck were treated as follows: after ipsilateral neck dissection with temporary protection of the jugular vein and carotid arteries, the neck remained open while transoral laser surgery of the primary tumor was performed. Pharyngeal defects were subsequently closed by either primary suture or a platysma myofascial flap. All patients underwent adjuvant radiotherapy. RESULTS: All primary tumors were completely resected. None of the patients required tracheotomy or placement of a percutaneous endoscopic gastrostomy tube. The mean duration of nasogastric feeding tubes was 12.7 days. In one case, the routine radiological contrast study revealed a blind cervical fistula 10 days after surgery. This healed spontaneously within 7 days. One mild postoperative hemorrhage had to be stopped by endoscopic coagulation under general anesthesia. During a mean follow-up of 19.4 months, none of the patients developed a local and/or regional recurrence. CONCLUSION: The surgical procedure described ensures sufficient protection of neck vessels during and after the transoral resection of advanced carcinomas of the pharynx. It successfully combines the advantages of minimally invasive laser microsurgery with those of flap reconstruction known from traditional surgery.

The role of biofilm infection in urology.

In the process of endourological development a great variety of foreign bodies have been invented besides urinary catheters on which biofilm can be formed. Bacteria in the biofilm are less sensible to antibiotics. An additional problem of medical biomaterials in the urinary tract environment is the development of encrustation and consecutive obstruction. In this review, we tried to sum up the conditions where biofilm formation has a great impact on the development or maintenance of urological infections and on treatment success. Modification of the biomaterial surface seems to be the most promising prevention strategy for bacterial biofilms. Easier methods for diagnosing and quantifying biofilm infection, to develop more specific antimicrobial agents and ideal device surfaces would surely help the fight against biofilm formation.

[Parinaud's oculoglandular syndrome. A rare differential diagnosis of "red eye"]. / Okuloglanduläres Syndrom nach Parinaud. Seltene Differenzialdiagnose des "roten Auges".

Two cases of Parinaud's oculoglandular syndrome, which represents an ocular manifestation of cat-scratch disease, are reported. The symptoms are subacute and include unilateral conjunctivitis and pre-auricular lymphadenopathy. Diagnosis primarily relies on the recognition of suggestive clinical signs in conjunction with positive serologic testing. In most cases, therapy is not necessary.

The role of TTF-1 in differentiating primary and metastatic lung adenocarcinomas.

Thyroid transcription factor-1 (TTF-1) is a sensitive marker for pulmonary and thyroid adenocarcinomas. The aim of this work was to determine its usefulness in distinction between primary and metastatic lung adenocarcinomas. We have examined the expression of TTF-1 in 100 solitary pulmonary nodules. They included 50 stage I peripheral primary bronchial adenocarcinomas (30 men, 20 women, mean age: 60 years) and 50 metastatic pulmonary adenocarcinomas (21 men, 29 women, mean age: 57 years) of different origins, such as breast (13), colon (13), rectum (13), kidney (7), stomach (2), and thyroid gland (2). TTF-1 immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues. In primary bronchial adenocarcinomas we found immunopositivity in 46/50 cases, among them 30 cases showed strong nuclear immunostaining. In four primary adenocarcinoma cases the observed immunopositivity was localized to the cytoplasm. Out of the metastatic adenocarcinomas all but the 2 thyroid cancers were negative. Both thyroid tumors showed strong immunopositivity. Our results confirm that TTF-1 immunohistochemistry is a very sensitive and highly specific method in the differential diagnosis of primary and metastatic lung adenocarcinomas and should be used in the everyday clinical practice.

[Solitary neurofibroma of the parapharyngeal space]. / Solitäres Neurofibrom im Parapharyngealraum.

A 21 year old male patient presented with dysphagia. Clinical examination as well as CT and MRT showed a tumor in the right parapharyngeal space. The tumor was resected completely using a transcervical approach. The pathological examination showed a neurofibroma. In this case report, preoperative diagnosis, therapy and follow-up of this rare tumor are discussed.

[Tonsillectomy by CO@ laser microsurgery--an analysis of clinical and morphological data]. / Die mikrochirurgische Tonsillektomie mit dem CO2-Laser. Eine Analyse klinischer und morphologischer Daten.

BACKGROUND: Tonsillectomy by CO(2) laser microsurgery is an almost bloodless procedure that has developed to an alternative to traditional dissection tonsillectomy during recent years. It has been suggested that the laser technique more precise than the conventional one, however, attempts to investigate this morphologically have not yet been undertaken. In addition, there is a need for large clinical studies to compare the postoperative bleeding risk of both procedures. METHODS: The charts of 617 patients who underwent routine tonsillectomy between 1995 and 1998 at the ENT department of Darmstadt Hospital, were retrospectively investigated with regard to postoperative bleeding events. A total of 467 patients were treated by the conventional technique and 150 by CO(2) laser microsurgery (continuous mode, 5 W). Moreover, 2 mm serial sections of tonsils of 56 consecutive patients treated in 1999 (31 conventional and 25 laser tonsillectomies) were used to determine peritonsillar (Vp) and tonsillar tissue volumes (Vt). RESULTS: The postoperative bleeding risk following laser tonsillectomy differed slightly from that following the conventional technique (12.0% vs 14.6%; P=0.499; Fisher's exact test). However, the incidence of severe bleeding events requiring revision in general anesthesia was significantly reduced (0.7% vs 4.9%; P=0.015; Fisher's exact test). Tonsillar specimens that were removed by laser surgery contained significantly less peritonsillar tissue than those from conventional procedures (Vp/Vt 5.1%+/-0.6% vs 10.8%+/-1.1%; P below 0.001; Mann-Whitney U-test). CONCLUSION: CO(2) laser microsurgery improves the precision of tonsillectomy and provides a maximum protection for the peritonsillar tissue. The incidence of severe bleeding events is markedly reduced. Laser tonsillectomy is therefore recommended for patients with clotting disorders or those requiring a particularly exact preparation technique.

Effect of keratinocyte growth factor on the proliferation, clonogenic capacity and colony size of human epithelial tumour cells in vitro.

PURPOSE: The effect of recombinant human keratinocyte growth factor (rHuKGF) on the proliferation, clonogenic capacity and colony size of low-passage human epithelial tumour cells was tested in vitro. MATERIALS AND METHODS: Five tumour cell cultures derived from head and neck squamous cell carcinomas, three cultures derived from pleural effusions of carcinomas of different origin and normal human nasal epithelial cells were analysed in passages 2-4. Expression of FGF7 and its receptor (FGFR2) were determined by the RNase protection assay. Cells were incubated with rHuKGF (10-200 ng ml(-1)) 3 days before or immediately after plating for clonal growth in serum-depleted media. To determine cellular radiosensitivity, single doses of 1-8 Gy X-rays were applied. Colony formation as well as colony size, reflecting the number of cell divisions, was determined after 10-15 days of growth in rHuKGF-treated and control cells. RESULTS: Normal nasal epithelial cells showed a two- to threefold increase in the number of cell divisions due to rHuKGF-treatment. In tumour cell cultures, significant stimulation of proliferation occurred in only one of eight samples. Tumour cells expressed FGF7 mRNA and protein, and low levels of FGFR2 mRNA. The addition of rHuKGF to the medium of the tumour cell cultures influenced neither radiation-induced impairment of proliferation nor clonogenic cell survival. CONCLUSION: rHuKGF has been shown to ameliorate the radiation tolerance of normal epithelia. The minimum in vitro tumour cell response to rHuKGF compared with normal epithelial cells suggests a potential for selective protection of normal epithelia during radiotherapy. The low FGFR2 expression as well as the FGF7 expression in the tumour cells may contribute to their resistance to rHuKGF treatment.

Clinical relevance of Fas (APO-1/CD95) expression in laryngeal squamous cell carcinoma.

BACKGROUND: Expression of Fas receptors renders tumor cells potentially susceptible to the host immune system. In squamous cell carcinomas of the head and neck, Fas has recently been found to be down-regulated in some cases; its prognostic value and correlation with clinicopathologic parameters, however, is yet to be delineated. METHODS: Paraffin-embedded specimens of 88 primary laryngeal squamous cell carcinomas were investigated for Fas protein expression by immunohistochemistry. Apoptotic tumor cells were visualized using the nick end labeling method. To assess the immunologic reaction to the neoplasm, the intensity of lymphoplasmocytic stroma reaction was determined. The mean follow-up time amounted to 45.9 months (range, 1-144 months). RESULTS: In tumor-adjacent normal mucosa and in most well-differentiated tumors, Fas expression was restricted to basal and parabasal cell layers. A diffuse pattern of staining reactions predominated in high-grade lesions (p <.001). The degree of Fas expression revealed a positive relationship with the intensity of lymphoplasmocytic stroma reaction (p =.002) but was unrelated to clinicopathologic parameters and to apoptotic rates of tumors. Neither Fas nor the lymphoplasmocytic stroma reaction had any impact on patient survival. CONCLUSIONS: Up-regulation of cell surface Fas expression in laryngeal carcinoma seems to have a stimulatory effect on the immune cell infiltration of the stromal tissue. Its lack of clinical relevance might be due to an inhibition of intracellular Fas signal transduction, which represents a frequent strategy of tumor cells to escape Fas-mediated apoptosis.

Radiotherapy combined with simultaneous chemotherapy with mitomycin-C and 5-fluorouracil for inoperable head and neck cancer.

The feasibility and effectiveness of a combined chemoradiotherapy treatment modality for locally advanced head and neck cancer was tested in a phase II trial. From March 1995 to June 1998, 35 patients with advanced squamous cell carcinoma of the head and neck were treated with a continuous intravenous infusion of 5-fluorouracil (600 mg m-2 24 h-1 for Days 1 to 5 (120 h)) and mitomycin-C (10 mg m-2 intravenously) on Day 5 during the first week of radiotherapy and on Day 36. 31 patients had stage IV disease; 4 patients had stage III; and 1 patient had stage II. Patient ages ranged from 42-69 years (median 56.7 years). The tumours involved were as follows: oral cavity (n = 11); oropharynx (n = 14); hypopharynx/larynx (n = 10). Radiotherapy was delivered to a total dose of 70 Gy with conventional fractionation (2 Gy per fraction, five times a week). Chemotherapy was well tolerated and all patients received the intended dose. Mild nausea occurred in five patients. After a mean follow-up of 21 months (range 10-44 months), 8 (23%) patients remain alive. A complete response was seen in 28 (80%) patients. When a recurrence appeared, it was within the first year after treatment. 1- and 2-year overall survival rates were 46% and 23%, respectively. Grade 3 mucositis occurred in 17% of patients. Grade 1-2 thrombopaenia occurred in 3 (9%) patients, grade > 2 leukopaenia in 4 (11%) patients, and grade > or = 2 anaemia in 3 (9%) patients. We observed a treatment interruption of maximum 1 week for six patients owing to mucositis. Febrile neutropaenia or aplasia were not observed. The concomitant use of 5-fluorouracil, mitomycin-C and radiotherapy in locally advanced head and neck carcinoma is well tolerated in this group of patients. This protocol showed good locoregional response with a very low toxicity profile.

[Prognostic significance of expression of p53, bcl-2 and bax in squamous epithelial carcinoma of the larynx--a multivariate analysis]. / Prognostische Bedeutung der Expression von p53, bcl-2 und bax im Plattenepithelkarzinom des Larynx--Eine multivariate Analyse.

BACKGROUND AND OBJECTIVE: Conventional clinicopathologic parameters do not accurately reflect the clinical outcome of patients with head and neck carcinoma. The establishment of additional prognostic factors that may give insight into the biologic features of a tumor is therefore an essential goal. The present study analyses the expression patterns of p53, bcl-2, and bax with regard to their relationships with conventional tumor parameters and to their prognostic significance in patients with laryngeal squamous cell carcinoma. PATIENTS/METHODS: Paraffin-embedded tissue sections of 88 primary laryngeal squamous cell carcinomas diagnosed and treated between 1986 and 1996 were investigated for p53, bcl-2, and bax protein expression by immunohistochemistry. The mean follow-up time was 45.9 months. RESULTS: Bcl-2 immunoreactivity was positively correlated with an advanced clinical stage, a high T category, regional lymph node metastasis, and a high histological grading. Significant relationship between clinicopathologic parameters and p53 or bax expression were not detectable. The age of the patients, advanced disease, positive bcl-2 expression, and a high level of p53 expression were significantly associated with shortened disease-specific survival in univariate analysis. In multivariate analysis, age, clinical stage, and p53 expression had independent prognostic value. CONCLUSIONS: Although expression of p53 and bcl-2 was found to be clinically relevant in univariate analysis, only p53 but not bcl-2 was an independent predictor of patient outcome. This superiority of p53 in multivariate analysis points to its central role within cell cycle and death regulation, with which it influences two important parameters of tumor progression.