Richard A. Lindtner

Bone-implant interface strength and osseointegration: Biodegradable magnesium alloy versus standard titanium control.

Previous research on the feasibility of using biodegradable magnesium alloys for bone implant applications mainly focused on biocompatibility and corrosion resistance. However, successful clinical employment of endosseous implants is largely dependent on biological fixation and anchorage in host bone to withstand functional loading. In the present study, we therefore aimed to investigate whether bone-implant interface strength and osseointegration of a novel biodegradable magnesium alloy (Mg-Y-Nd-HRE, based on WE43) is comparable to that of a titanium control (Ti-6Al-7Nb) currently in clinical use. Biomechanical push-out testing, microfocus computed tomography and scanning electron microscopy were performed in 72 Sprague-Dawley rats 4, 12 and 24 weeks after implantation to address this question. Additionally, blood smears were obtained from each rat at sacrifice to detect potential systemic inflammatory reactions. Push-out testing revealed highly significantly greater maximum push-out force, ultimate shear strength and energy absorption to failure in magnesium alloy rods than in titanium controls after each implantation period. Microfocus computed tomography showed significantly higher bone-implant contact and bone volume per tissue volume in magnesium alloy implants as well. Direct bone-implant contact was verified by histological examination. In addition, no systemic inflammatory reactions were observed in any of the animals. We conclude that the tested biodegradable implant is superior to the titanium control with respect to both bone-implant interface strength and osseointegration. These results suggest that the investigated biodegradable magnesium alloy not only achieves enhanced bone response but also excellent interfacial strength and thus fulfils two critical requirements for bone implant applications.

Intramural and extramural vascular invasion in colorectal cancer: prognostic significance and quality of pathology reporting.

Blood vessel invasion has been associated with poor outcome in colorectal cancer (CRC), whereas the prognostic impact of lymphatic invasion is less clear. The authors of this report evaluated venous and lymphatic invasion as potential prognostic indicators in patients with CRC focusing on lymph node‐negative patients and compared routine and review pathology diagnoses.

Tumor necrosis is a new promising prognostic factor in colorectal cancer

The prognostic significance of tumor necrosis in colorectal cancer is unclear. Our study aimed to analyze the prognostic value of tumor necrosis with respect to progression-free and cancer-specific survival and to relate findings to expression of proteins involved in the control of cancer cell death, such as p53 and bcl-2. A total of 381 colorectal cancer specimens were retrospectively reevaluated. The extent of tumor necrosis was semiquantitatively assessed and recorded as either absent, focal (≤10% of the tumor area), moderate (10%-30%), or extensive (≥30%). Expression of p53 and bcl-2 was assessed immunohistochemically and recorded as either positive (using a cutoff value of 10%) or negative. In addition, mismatch repair protein status was assessed by immunohistochemistry using antibodies directed against hMLH1, hMSH2, and hMSH6. Tumor necrosis was observed in 365 (96%) cases, with 180 (47%) tumors showing focal necrosis, 119 (31%) moderate necrosis, and 66 (17%) extensive necrosis, respectively. Extent of necrosis was significantly associated with high T classification (P < .001), high N classification (P = .005), high International Union Against Cancer stage (P < .001), poor tumor differentiation (P < .001), large tumor size (P < .001), and blood vessel invasion (P = .01). No association of tumor necrosis with expression of p53, bcl-2, and mismatch repair protein status was observed. Tumor necrosis proved to be an independent prognostic variable with respect to progression-free and cancer-specific survival. In conclusion, tumor necrosis showed significant impact on prognosis of colorectal cancer patients. Its presence is readily assessable in hematoxylin and eosin-stained sections and should therefore routinely be commented upon in the pathology report.

Value of tumor size as a prognostic variable in colorectal cancer: a critical reappraisal.

Objectives: Vertical tumor growth, reflected by T classification, represents the most important prognostic variable in colorectal cancer. Our study aimed to investigate the impact of tumor size, particularly the maximum tumor diameter, on outcome of affected patients. Methods: A total of 381 colorectal cancer specimens were re-evaluated. Tumor size and location were extracted from the medical history and were known for 359 patients (94%). Receiver-operator characteristic analysis was applied to identify the optimal (maximum of sum of sensitivity and specificity) cut-off values with respect to prognostic impact. Results: Median tumor size was 4.5 cm (range, 0.6–15). Tumor size exceeding 4.5 cm was observed in 159 patients (44%) and was associated with high T and N classification, UICC stage, and tumor grade. At median follow-up of 45 months (range, 0–180), 141 patients (40%) showed tumor progression. Although 4.5 cm was identified as the optimal cut-off value within the whole group of patients, receiver-operator characteristic analysis restricted to different parts of the large bowel determined 5 cm, 5.3 cm, 3.9 cm, and 3.4 cm as cut-off values with the strongest discriminatory capacity in colon, right-sided colon, left-sided colon, and rectum cancers, respectively. Applying these cut-off values, tumor size was significantly associated with progression-free and cancer-specific survival in univariate and multivariate analyses in colon, yet not in rectum cancers. Conclusions: Tumor size proved to be an independent prognostic parameter for patients with colorectal cancer. Optimal cut-off values vary among different parts of the large bowel. Whereas prognostic significance is strong within the colon, it appears to be of minor value within the rectum.

Mucinous differentiation in colorectal cancer – indicator of poor prognosis?

Langner C, Harbaum L, Pollheimer M J, Kornprat P, Lindtner R A, Schlemmer A, Vieth M & Rehak P 
(2012) Histopathology 60, 1060–1072

Combined posteroanterior fusion versus transforaminal lumbar interbody fusion (TLIF) in thoracolumbar burst fractures

BACKGROUND The optimal treatment strategy for burst fractures of the thoracolumbar junction is discussed controversially in the literature. Whilst 360° fusion has shown to result in better radiological outcome, recent studies have failed to show its superiority concerning clinical outcome. The morbidity associated with the additional anterior approach may account for these findings. The aim of this prospective observational study was therefore to compare two different techniques for 360° fusion in thoracolumbar burst fractures using either thoracoscopy or a transforaminal approach (transforaminal lumbar interbody fusion (TLIF)) to support the anterior column. METHODS Posterior reduction and short-segmental fixation using angular stable pedicle screw systems were performed in all patients as a first step. Monocortical strut grafts were used for the anterior support in the TLIF group, whilst tricortical grafts or titanium vertebral body replacing implants of adjustable height were used in the combined posteroanterior group. At final follow-up, the radiological outcome was assessed by performing X-rays in a standing position. The clinical outcome was measured using five validated outcome scores. The morbidity associated with the approaches and the donor site was assessed as well. RESULTS There were 21 patients in the TLIF group and 14 patients in the posteroanterior group included. The postoperative loss of correction was higher in the TLIF group (4.9°±8.3° versus 3.4°±6.4°, p>0.05). There were no significant differences regarding the outcome scores between the two groups. There were no differences in terms of return to employment, leisure activities and back function either. More patients suffered from donor-site morbidity in the TLIF group, whilst the morbidity associated with the surgical approach was higher in the posteroanterior group. CONCLUSION The smaller donor-site morbidity in the posteroanterior group is counterbalanced by an additional morbidity associated with the anterior approach resulting in similar clinical outcome. Mastering both techniques will allow the spine surgeon to be more flexible in specific situations, for example, in patients with neurological deficits or severe concomitant thoracic trauma.

Comparative biomechanical and radiological characterization of osseointegration of a biodegradable magnesium alloy pin and a copolymeric control for osteosynthesis

Magnesium alloys offer great advantages as degradable implant material for pediatric fracture fixation and hold the potential to overcome certain critical shortcomings inherent to currently used degradable (co)polymers. Besides good biocompatibility and appropriate degradation kinetics, sufficient implant anchorage in host bone is critical to prevent implant failure. Bone-implant anchorage of biodegradable magnesium alloys, however, has not yet been related and compared to that of copolymers, their degradable counterparts currently in clinical use. The aim of this study, therefore, was to comparatively assess bone-implant interface strength and the amount of peri-implant bone of a biodegradable magnesium alloy pin (Mg-Y-Nd-HRE) and a self-reinforced copolymeric control (85/15 poly(l-lactic-co-glycolic acid)). To this purpose, push-out testing, microfocus computed tomography (μCT), histological and scanning electron microscopic examination was performed after 4, 12 and 24 weeks of transcortical implantation in 72 rats. Biomechanical testing revealed significantly higher ultimate shear strength for the magnesium alloy pins than for the copolymeric controls at all 3 timepoints (P≤0.001 for all comparisons). As evaluated by μCT, the amount of bone present near the interface and in a wider radius (up to 0.5mm) around it was higher in the magnesium alloy implants at 4 weeks, without significant differences at 12 and 24 weeks. Histological examination confirmed direct bone-to-implant contact for both implant types. In vivo degradation of implants did not induce any noticeable local or systemic inflammation. This data suggests that the investigated degradable magnesium alloy rod exhibits markedly superior bone-implant interface strength and a greater amount of peri-implant bone than a self-reinforced copolymeric control currently in use; thus it fulfills a crucial prerequisite for its successful clinical deployment as an alternative degradable orthopedic implant material. Further studies, however, are warranted to evaluate the long-term degradation behavior and biocompatibility of the investigated degradable magnesium-based alloy.

Keratin 7 expression in colorectal cancer--freak of nature or significant finding?

Harbaum L, Pollheimer M J, Kornprat P, Lindtner R A, Schlemmer A, Rehak P & Langner C 
(2011) Histopathology59, 225–234

Clinicopathological significance of prolactin receptor expression in colorectal carcinoma and corresponding metastases

The role of human prolactin and its receptor, the prolactin receptor, in colorectal cancer is largely unknown. Our study aimed to assess the prevalence of prolactin receptor expression, its association with clinicopathological variables, as well as its prognostic value, comparing results of primary tissues with those of corresponding metastases. In all, 373 primary colorectal cancer and 171 corresponding metastases were evaluated for prolactin receptor expression by immunohistochemistry using a tissue microarray technique. Immunoreactivity was semiquantitatively scored as either focal (<10% of tumor cells positive), moderate (10–50%), or extensive (>50%). Prolactin receptor expression was related to clinicopathological parameters as well as patient outcome. To substantiate our findings, prolactin receptor expression was additionally assessed in HT-29 and SW-480 colorectal cancer cell lines using western blot. Prolactin receptor expression was observed in 360 out of 373 (97%) primary tumors, with 21 (6%) cases showing focal, 55 (15%) moderate, and 284 (76%) extensive expression, respectively. Extensive prolactin receptor expression was significantly associated with tumor size (P=0.002) and grade (P<0.001) as well as histological subtype (P<0.001). Somer’s D coefficients for concordance of primary tumors with corresponding lymph node and distant metastases were D=0.719 (P<0.001) and D=0.535 (P=0.001), respectively. Extensive prolactin receptor expression was significantly associated with disease progression (P=0.03) and cancer-specific survival (P=0.04) in patients with high-grade cancers. In conclusion, prolactin receptor expression is common in colorectal cancer, with high concordance between primary tumors and corresponding metastases. In view of evolving targeted therapy concepts in colorectal cancer, widespread prolactin receptor expression may offer a therapeutic perspective in affected patients.

Characterization methods of bone–implant-interfaces of bioresorbable and titanium implants by fracture mechanical means

Bioresorbable materials for implants have become increasingly researched over the last years. The bone-implant-interfaces of three different implant materials, namely a new bioresorbable magnesium alloy, a new self-reinforced polymer implant and a conventional titanium alloy, were tested using various methods: push-out tests, SEM and EDX analyses as well as surface analyses based on stereoscopic 3D pictures were conducted. The fracture energy is proposed as a very significant reference value for characterizing the mechanical performance of a bone-implant system. By using a video-extensometer system instead of, as is commonly done, tracking the movement of the crosshead in the push-out tests, the accuracy of measurement could be increased.