Experimental findings on customized mandibular implants in Göttingen minipigs - a pilot study.

Reconstructing continuity defects of the mandible is still challenging for surgeons. The currently applied conventional titanium bridging plates have considerable rates of complications. Now, a new technology enables an individual shape-identical creation of a mandibular implant in a form-board design by the method of LaserCUSING using pure titanium. This technology has been successfully performed in previous examinations to individually reconstruct mandibular continuity defects. This pilot study evaluated the surgical procedure in 10 female Göttingen mini pigs. First, a computed tomography scan from a mini pig cranium was performed. A three-dimensional model of the mandible was designed by data conversion. Based on the data, a customized mandibular implant resembling the natural shape was virtually created and manufactured. Then, a continuity defect of the left mandible was created in a standardized way. The implants were inserted into the defect and the wounds were allowed to heal for 21, 35, 56 and 180 days. During the healing period, no signs of inflammation or infection were observed. After the sacrifice of the minipigs the mandibles were resected. Histological microsections using Donath's sawing and grinding technique were manufactured and stained with Masson Goldner trichrome staining. The histomorphological results showed a pronounced ossification at the outer and inner surface of the implants. This animal study describes a promising approach to optimize customized implants for the application in humans.

[Computed tomography evaluation of human mandibles with regard to layer thickness and bone density of the cortical bone]. / Computertomografische Auswertung von humanen Unterkiefern hinsichtlich der Schichtstärke und Knochendichte der Kortikalis.

PURPOSE: Application of function-restoring individual implants for the bridging of defects in mandibles with continuity separation requires a stable fixation with special use of the cortical bone stumps. MATERIALS AND METHODS: Five section planes each of 100 computed tomographies of poly-traumatized patients' jaws were used for measuring the thickness of the cortical layer and the bone density of the mandible. The CT scans of 28 female and 72 male candidates aged between 12 and 86 years with different dentition of the mandible were available. RESULTS: The computed tomographic evaluations of human mandibles regarding the layer thickness of the cortical bone showed that the edge of the mandible in the area of the horizontal branch possesses the biggest layer thickness of the whole of the lower jaws. The highest medians of the cortical bone layer thickness were found in the area of the molars and premolars at the lower edge of the lower jaws in 6-o'clock position, in the area of the molars in the vestibular cranial 10-o'clock position and in the chin region lingual-caudal in the 4-o'clock position. The measurement of the bone density showed the highest values in the 8-o'clock position (vestibular-caudal) in the molar region in both males and females. CONCLUSION: The average values available of the bone density and the layer thickness of the cortical bone in the various regions of the lower jaw, taking into consideration age, gender and dentition, are an important aid in practice for determining a safe fixation point for implants in the area of the surface layer of the mandible by means of screws or similar fixation elements.

Free DIEP-flap reconstruction of tumour related defects in head and neck.

The free deep inferior epigastric perforator flap (DIEP) is a well-established therapy for plastic reconstruction of the breast or defects of the lower extremity without distinct donor site morbidity. Because of its particular qualities we started to apply the DIEP-flap also in reconstruction of defects in the cranio-maxillofacial area. A series of 10 consecutive patients, who received a DIEP-flap for reconstruction of large soft tissue defects after ablative tumour surgery, was reviewed. Nine of the 10 flaps survived and uneventfully healing was observed in 8 of the 10 flaps. Primary layered closure of the abdominal wall was achieved in all cases and no complications at the donor site were observed. In our experience the DIEP may serve as a well considerable alternative to the rectus abdominis flap and the latissimus dorsi flap for bridging extensive reconstructions in the cranio-maxillofacial region. It offers the possibility for flap elevation simultaneously to the surgical procedures in the head and neck area. A special advantage of the DIEP-flap is the very low donor site morbidity.

[Exsudativ proliferative synovialitis of the temporomandibular joint]. / Exsudativ proliferative Synovialitis des Kiefergelenkes.

A 39-year-old male patient suffered from pain in the right temporo-mandibular-joint (TMJ) region for more than one year particular when chewing. He was suspected of having a parotis gland tumor and was admitted to the ENT Department. Three months prior to admission there was an increasing swelling. MRT contrast enhanced scan proofed a partly cystic partly soft tissue dense tumor in the regions of the masseter and pterygoideus medialis muscles and the cranial parts of the parotic gland. Ultrasound scan confirmed these findings and showed in addition a suspect lymph node at level II. Electroneurography of the facial nerve was without pathology. Biopsies revealed no pathologies. With persisting pain the patient was transferred to the Department of Oral and Maxillofacial Surgery. History and clinical examination revealed: regular use of chewing gum for several years, pain and clicking in the TMJ and use of a dental splint without relief after removal of the wisdom teeth 28 and 38. Special radiographic diagnostics did not show any pathology but the swelling was persisting. Open joint surgery and histology proofed a chronic synovialitis of the TMJ. In the follow-up after 7 months the patient was free of pain and complaints. This case demonstrates the necessity of interdisciplinary collegial communication to optimally treat patients that suffer from pathologies at the borders of the specialised fields in the head and neck region.

Prediction of gastric cancer lymph node status by sentinel lymph node biopsy and the Maruyama computer model.

AIMS: The extent of lymph node dissection in gastric cancer remains controversial. The Maruyama computer model and the sentinel lymph node biopsy (SLNB) are compared for their value to predict the nodal status and lead to stage-adapted surgery. METHODS: Thirty four patients with stage I-IV gastric cancer underwent both staging procedures. For SLNB, 15 patients underwent endoscopic, peri-tumoural injection of (99m)Tc-colloid, and 19 patients were injected of Patent blue V. All 'hot' or blue sentinel lymph nodes (SLNs) were separately excised and histopathologically assessed. If the SLN was negative after routine staining by H&E, it was processed completely and reanalysed after immunohistochemistry. RESULTS: At least, one SLN was detected by means of SLNB in 33/34 of the patients. The sensitivity to identify a positive nodal status was 22/33 and the specificity/positive predictive value was 10/10 and 22/22. Additional micrometastases or isolated tumour cells in the SLN led to 'upstaging' of 5/15, initially classified as nodal negative by H&E-staining. Using the Maruyama computer model, a sensitivity of 22/23 for the correct prediction of the lymph node involvement was associated with a specificity of 2/10 and a positive predictive value of 22/30. CONCLUSIONS: The clinical impact of the Maruyama computer model is limited due to low specificity and a low positive predictive value, rendering the method less useful as an indicator for individualised surgery.

Growth rate and cell size modulate the synthesis of, and requirement for, G1-phase cyclins at start.

In Saccharomyces cerevisiae, commitment to cell cycle progression occurs at Start. Progression past Start requires cell growth and protein synthesis, a minimum cell size, and G(1)-phase cyclins. We examined the relationships among these factors. Rapidly growing cells expressed, and required, dramatically more Cln protein than did slowly growing cells. To clarify the role of cell size, we expressed defined amounts of CLN mRNA in cells of different sizes. When Cln was expressed at nearly physiological levels, a critical threshold of Cln expression was required for cell cycle progression, and this critical threshold varied with both cell size and growth rate: as cells grew larger, they needed less CLN mRNA, but as cells grew faster, they needed more Cln protein. At least in part, large cells had a reduced requirement for CLN mRNA because large cells generated more Cln protein per unit of mRNA than did small cells. When Cln was overexpressed, it was capable of promoting Start rapidly, regardless of cell size or growth rate. In summary, the amount of Cln required for Start depends dramatically on both cell size and growth rate. Large cells generate more Cln1 or Cln2 protein for a given amount of CLN mRNA, suggesting the existence of a novel posttranscriptional size control mechanism.

Sentinel lymph node biopsy in rectal cancer--not yet ready for routine clinical use.

BACKGROUND: The value of sentinel node biopsy in visceral cancers is uncertain. We evaluated the feasibility and utility of radiocolloid lymphatic mapping and selective lymph node sampling in patients with rectal cancer. METHODS: Forty-eight patients with rectal cancer were investigated. Thirty-seven patients had already undergone preoperative radiochemotherapy for locally advanced tumors. Eleven patients underwent primary surgery. An endoscopic injection of 1 mL technetium 99m-sulfur-colloid into the peritumoral submucosa was performed 15 to 17 hours before surgery. Ex vivo identification of the nuclide-enriched "sentinel lymph nodes" (SLNs) was performed using a hand-held gamma-probe. The selected SLNs were then carefully and systematically examined using serial sections and immunohistochemistry. RESULTS: One or more SLNs were found in 46 of the 48 patients. The SLN detection rate was 96%. Sixteen of the 48 patients had lymph node metastases (35%). In 7 of the 16 patients, the SLNs correctly represented the nodal status. In 9 of the 16 patients, the SLN was tumor-free whereas non-SLN harbored metastases. This result represents a sensitivity of only 44%, and a false-negative rate of 56%. Further analysis showed that the method correctly predicted the nodal status only in the small subgroup of 5 patients with early cancer without preoperative radiation. In 4 patients, juxtaregional lymph nodes were excised on the basis of intraoperative radiocolloid detection, leading to upward staging in 1 patient. CONCLUSIONS: Sentinel lymph node biopsy using the radiocolloid technique with ex vivo lymph node identification shows a relatively high detection rate; however, the sensitivity in patients with locally advanced/irradiated rectal cancer is low. Nevertheless, the detection of juxtaregional metastases can improve staging in some patients. Further studies should focus on patients with early rectal cancers where the data were more promising.

Sentinel node biopsy in anal cancer - a promising strategy to individualize therapy.

BACKGROUND: In order to individualize the therapy in patients with anal cancer, we evaluated the applicability of the sentinel lymph node (SLN) concept for the staging of inguinal lymph nodes in these patients. PATIENTS AND METHOD: SLN mapping using the radiocolloid technique was performed in 12 patients with histopathologically proven anal cancer. Mean age of the 4 male and 8 female patients was 62 years (range: 37-83 years). All patients underwent injection of (99m)Tc-colloid (Nanocis) in 4 portions around the tumor followed by scintigraphy after 17 h and selective lymph node biopsy in case of nuclide enrichment. The nuclide-enriched lymph node was intraoperatively identified by a hand-held gamma-camera. Histopathological assessment of the harvested SLNs included serial sections and immunohistochemical staining. RESULTS: Enrichment of radiocolloid in lymph nodes was seen in 10 of the 12 patients (detection rate: 83%). SLN biopsy was performed in 9 patients, one patient refused the SLN biopsy (SLNB). 4 patients revealed tumor-infiltrated sentinel lymph nodes including one patient with bilateral biopsy, who showed metastases unilaterally. The remaining 5 patients had no evidence of metastases in the excised SLNs. CONCLUSION: It is feasible to evaluate the nodal status of the groin in patients with anal cancer using the radiocolloid technique. Preliminary results indicate a refined diagnostic work-up for anal cancer patients, potentially improving the results of clinical and sonographical examinations. Further application of the method may lead to an individualized treatment of patients with anal cancer.

[Lymphatic mapping and sentinel lymph node biopsy in gastric cancer]. / Lymphatic mapping und Sentinel-Lymphknotendiagnostik beim Magenkarzinom.

INTRODUCTION: Lymphatic mapping and the sentinel lymph node (SLN) concept has been validated in malignant melanoma and breast cancer.However, the application for other solid tumors is still controversial. One of the most promising approaches is selective lymph node staging in gastric cancer.The presented pilot study evaluated the feasibility of the radiocolloid technique in gastric cancer patients and its value in predicting a positive nodal status. PATIENTS AND METHODS: Fifteen patients with gastric cancer (u T(1-3)) underwent endoscopic submucosal injection of 0.4 ml 60 MBq (99m)Tc-Nanocis around the tumor 17 (+/-3) h prior to surgery. After laparotomy the activity of all 16 (JGCA) lymph node stations was measured by a handheld probe. All patients underwent standard gastrectomy with systematic D2 lymphadenectomy. After resection the site was scanned for residual activity. All sentinel lymph nodes (SLN's) were removed ex vivo from the resected specimen and processed for intensified histopathologic assessment including serial sections and immunohistochemistry. RESULTS: In 14 of 15 patients at least one or more SLN's were obtained (93%), the median number of SLN's was 3 (1-5). Of the 14 patients, 9 revealed lymph node metastases. In eight of the nine patients the sentinel node(s) correctly predicted metastatic lymph node invasion. In five cases the lymph node station with positive sentinel node(s) was the only positive node station resulting in a sensitivity of 8/9 (89%). In one case immunohistochemical staining revealed micrometastases leading to an upstaging in 1/6 of the initially nodal-negative patients. CONCLUSION: Lymphatic mapping and sentinel node biopsy using the radiocolloid technique is feasible in gastric cancer. Limited results indicate a correct prediction of the nodal status and the potential of upstaging.Further studies seem to be justified to evaluate the clinical impact of the method.

Sentinel lymphonodectomy in gastrointestinal cancer--where are we now?

Up to now, no reliable methods for the pre- or intraoperative prediction of the nodal status are available in gastrointestinal cancer patients. Therefore, after the successful application of the sentinel lymph node concept in melanoma and breast cancer, ongoing research on this field is extended to gastrointestinal tumor entities. According to recent experiences, the most promising tumor entities are colon, gastric and anal cancer. First results with these patients indicate that the method could be a reliable predictor of the nodal status and, thus, may have important future implications for adjuvant therapy and the extent of surgery. The dye method for colon cancer and the combined method (dye and radiocolloid) for gastric cancer seem to be appropriate approaches, even when the general experience is still low. In rectal cancer, however, current experience failed yet to yield satisfying results. Up to now, anal cancer has not been a focus of publication, even when the concept seems to be very attractive for the evaluation of the inguinal lymph node status.

Lymphatic mapping and retrieval of the sentinel lymph node in treatment of early breast cancer.

Lymphatic mapping and sentinel lymph node biopsy is an important step to surgical individualization of breast cancer therapy. With lymphatic mapping and minimally invasive biopsy of one or two detected lymph nodes the method provides an exact evaluation of the nodal status. Using sentinel lymph node biopsy (SLNB), costs and morbidity of an axillary lymph node dissection (ALND) can be avoided in nodal negative patients, whereas nodal positive patients are chosen for ALND very selectively according to the detection of an increased percentage of micrometastases. While experienced centers are introducing this method into clinical practice for the benefit of patients with early-stage breast cancer in Europe, further research should focus on quality control, definition of standards considering the individual needs of the individual patient, and the evaluation of the impact of micrometastases. This article gives an overview of the current knowledge of SLNB and discusses critically current indications and methods as well as application techniques.

["Sentinel" lymph node biopsy in breast carcinoma. Current experiences]. / "Sentinel"-Lymphknotenbiopsie beim Mammakarzinom. Aktuelle Erfahrungen.

Recent studies show the sentinel lymph node biopsy (SNB) as a reliable method for the determination of the nodal status in patients with breast cancer. We present our experience with this method during 3 years and discuss its potential and limitations. From 11/95 to 3/99 we performed a sentinel node detection in 146 patients with breast cancer stage I to III. We used the raionuclide method including preoperative lymphscintigraphy and intraoperative gamma.probe detection. The detection rate varied with the tumor size between 94% for tumors with a diameter < 1 cm, 85% (1-3 cm), 70% (3-5 cm) and 63% (> 5 cm). The accuracy of the SNB in the prediction of the nodal status varied also with the tumor diameter between 100% for very small tumors (< 1 cm), 97% (1-3 cm), 88% (3-5 cm) and 67% (> 5 cm). In the subgroup of patients restricted to T1-2-tumors (n = 106), 57 patients (53%) showed true negative, 4 (4%) false negative SNB. 38 (36%) revealed tumor cells in the HE-staining and an additional 7 patients (7%) solely in the immunohistochemical staining. The presented results show, that SNB is a reliable method for the evaluation of the nodal status in early breast cancer patients with a tumor size up to ca. 3 cm. While in about 50% of these patients a surgical intervention could be avoided after a negative SNB, an additional 5-10% of conventionally nodal negative patients can be found by the immunohistochemical examination of the sentinel node. The sn-concept can also identify parasternal metastasis and can be applied in patients after neoadjuvant therapy and patients with recurrent tumor. Indications and contraindications of this method, however, still remain to be determined.

Sentinel lymph node dissection in breast cancer.

During the last years, the efficacy and reliability of the sentinel lymph node biopsy (snb) as a minimal invasive diagnostic procedure for the nodal status has been intensively evaluated. After the widespread clinical use in the staging of melanoma patients the snb is currently introduced in the clinical management of breast cancer patients. We present our experience with this method during 3, 5 years and discuss its potential and pitfalls. From 11/95 to 3/99 we performed sentinel node detection in 146 patients with breast cancer stage I to III, consisting of 127 patients with pT1/2-tumors and 19 patients with pT3/4-tumors. We used the radionuclid method including preoperative lymphoscintigraphy and intraoperative gamma-probe detection. The detection rate varied with the tumor size between 94% for tumors with a diameter < 1 cm, 85% (1-3 cm), 70% (3-5 cm) and 63% (> 5 cm). The accuracy of the snb in the prediction of the nodal status changed also with the tumor diameter between 100% for very small tumors (< 1 cm), 97% (1-3 cm), 88% (3-5 cm) and 67% (> 5 cm). In the subgroup of patients restricted to T1-2-tumors (n = 106). 57 patients (53%) showed true negative snb. 38 patients (36%) revealed tumor cells in the H&E-staining and an additional 7 patients (7%) solely in the immunohistochemical staining. 4 (4%) of these patients, all of them from the first half of the study period, underwent false-negative snb, 3 of them showing lymphangiosis carcinomatosa. The presented results show, that snb using the radionuclid method is a reliable method for the evaluation of the nodal status in early breast cancer patients with a tumor size up to ca. 3 cm. Therefore the sn procedure should be restricted to small tumors with clinically uninvolved axillary nodes or patients with a ductal carcinoma in situ (DCIS) to rule out invasiveness.

[Sentinel node detection in breast carcinoma]. / "Sentinel node detection" beim Mammacarcinom.

The aim of sentinel node biopsy (SN) in breast cancer patients is to detect the tumor-draining lymph node by means of isosulfan blue or 99mTc-labelled colloids. SN can be detected in 80 to 85% of the patients, depending on the size of the tumor. Preoperative lymphoscintigraphy permits the draining nodes along the internal mammary artery also to be visualized. The predictive value of the histological findings of SN for lymph nodes obtained from axillary dissection is about 95%. Because of different diagnostic procedures using various radiotracers each center has to follow its own learning curve. To be sure that the nodal status derived from a SN procedure is of identical value to axillary dissection about 100 patients have to undergo sentinel node detection, followed by axillary dissection, and concordant results should be obtained in 95% of them at least. The SN, however, offers a chance of assessing the lymph node at risk for metastasis by more detailed histological procedures. Morbidity as a result of treatment for primary breast cancer can be decreased if only patients suffering from metastatic disease are subjected to axillary dissection. Currently, the indication criteria for a SN procedure should be restricted to small tumors (T1) with clinically uninvolved axillary status and patients with ductal carcinoma in situ (DCIS).

[Axillary node removal in clinical node-negative breast carcinoma. Can its indication be individualized by "sentinel node" detection?]. / Axillaausräumung bei klinisch nodal-negativem Mammakarzinom. Kann die Indikation durch "sentinel node"-Nachweis individualisiert werden?

BACKGROUND AND OBJECTIVE: The status of the axillary lymph node(s) is an important prognostic factor in breast cancer and thus decisive in the indication for adjuvant treatment. This study investigated the extent to which examination of the sentinel node (SN) can individualize the need for axillary resection and the diagnosis of lymph nodes be optimized. PATIENTS AND METHODS: 96 consecutive patients with breast cancer were studied (94 women, 2 men; mean age 59 [36-84] years) in whom no lymph node enlargement had been diagnosed clinically. After preoperative lymph-drainage scintigraphy with 99mTc Nanocoll combined with intraoperative scintillation probe detection the SN node was identified in 77 of the 96 patients and was removed. Subsequently the axillary lymph nodes in level I and II were removed by a standard technique and all removed lymph nodes and material then compared histologically. RESULTS: In nine of 77 patients with identifiable SN it was the only lymph node with metastasis. In 18 patients both the SN and other axillary lymph nodes were infiltrated. The SN and other axillary lymph nodes were free of metastases in 44 patients. In six patients the SN was not representative, since it was free of tumour, but other axillary nodes were not. Identification of a SN and prognostication of lymphogenic axillary metastases depended on tumour size. Among T3 and T4 tumours, ten of 16 had a verifiable SN, but in six of them it was not representative for axillary metastasization. But in 62 of 73 patients with tumours up to 5 cm in diameter without involvement of skin or chest wall (T1 and T2, respectively) a SN could be identified that was not representative for axillary metastases in only two cases. CONCLUSIONS: SN resection in breast cancer makes it possible to individualize axillary node resection as part of primary treatment. Specific histological examination of serial sections and immunohistological testing may possibly increase the accuracy of histological diagnosis.

[Sentinel lymph node detection in patients with breast carcinoma]. / Die Sentinel Lymphknoten-Detektion bei Patienten mit Mammakarzinom.

Sentinel node detection enables the definition of the most relevant draining lymph node of a tumor. We analysed 123 patients with breast cancer according to this method. A preoperative lymphoscintigraphy was performed 17 hours after a peritumoral application of 0.5 ml 99mTC-Nanokoll. The sentinel node was identified by means of a gammaprobe in 75 of 89 patients with pT1- and pT2-tumors and in 11 of 17 patients with pT3-4 tumors respectively. The results of histological investigation of the sentinel node in comparison to all other axillary nodes following dissection were correlated. In the pT1-2 group the accuracy of correlative findings was rather high (96%). In patients with pT3- and pT4-tumors the lymph node status was predictable only in 7 patients. Therefore sentinel node biopsy may serve as a tool for individualization of axillary dissection especially in pT1-2 breast cancer patients.

[Diagnostic value of 123iodine-ibzm scintigraphy for staging of malignant melanomas]. / Diagnostischer Wert der 123Iod-IBZM-Szintigraphie zum Staging von malignen Melanomen.

AIM: We performed 123I-(S)-2-hydroxy 3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide (123I-IBZM)-scintigraphy to evaluate one usefulness of this radiopharmaceutic agent for the diagnosis of malignant melanomas. METHODS: We performed whole body scintigraphies after intravenous application of 123I-IBZM in 20 patients and compared the scintigraphic findings with the results of other imaging methods. RESULTS: In four patients no melanotic lesions were detectable, neither by 123I-IBZM-scintigraphy nor by other imaging procedures. A scintigraphic detection of cutaneous or subcutaneous lesions was possible in our of ten patients. 123I-IBZM-scintigraphy showed pathological findings in five of ten patients with lymph node metastases. Two patients had brain metastases, in four patients lung localizations were present. None of these organic manifestations was discovered by scintigraphic means. Amelanotic lesions never showed an accumulation of 123I-IBZM. It was not possible to detect any "new" lesions, i.e. lesions not visualized by other imaging procedures. CONCLUSION: 123I-IBZM-scintigraphy did not present additional information important for the therapy of patients with malignant melanoma.

[Quantitative radionuclide leakage control during isolated limb perfusion]. / Quantitative Leckkontrolle mit Radionuckliden bei der isolierten Extremitätenperfusion.

In order to reduce side effects of high-dose chemotherapy the penetration of the cytostatic substances into the main circulation should be prevented or limited. An efficient procedure for checking the leakage is generally based on the addition of a radionuclide to the perfusate. By scintillation probes the distribution of this radionuclide in the body of the patient is checked. A method is presented which continuously calculates the actual volume of the fluid which is penetrating into the main circulation during the perfusion. The values of momentary and cumulative volume crossover enables the surgical oncologist to detect a leakage readily and reliably and may be the basis for measures of confining it.